Review ArticleEthnopharmacological Significance ofEclipta alba (L) Hassk (Asteraceae)

Rownak Jahan1 Abdullah Al-Nahain2

Snehali Majumder3 and Mohammed Rahmatullah24

1 Department of Biotechnology amp Genetic Engineering University of Development Alternative Dhanmondi Dhaka 1209 Bangladesh2Department of Pharmacy University of Development Alternative Dhanmondi Dhaka 1209 Bangladesh3 Department of Microbiology and Serology NH Health Bangalore 560099 India4 Faculty of Life Sciences University of Development Alternative House No 78 Road No 11A (new) DhanmondiDhaka 1209 Bangladesh

Correspondence should be addressed to Mohammed Rahmatullah rahamatmhotmailcom

Received 29 June 2014 Accepted 8 September 2014 Published 29 October 2014

Academic Editor Jagadananda Ghosh

Copyright copy 2014 Rownak Jahan et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Eclipta alba can be found growing wild in fallow lands of Bangladesh where it is considered as a weed by farmers Traditionalmedicinal systems of the Indian subcontinent countries as well as tribal practitioners consider the plant to have diverse medicinalvalues and use it commonly for treatment of gastrointestinal disorders respiratory tract disorders (including asthma) fever hairloss and graying of hair liver disorders (including jaundice) skin disorders spleen enlargement and cuts andwoundsThe plant hasseveral phytoconstituents like wedelolactone eclalbasaponins ursolic acid oleanolic acid luteolin and apigenin Pharmacologicalactivities of plant extracts and individual phytoconstituents have revealed anticancer hepatoprotective snake venom neutralizinganti-inflammatory and antimicrobial properties Phytoconstituents like wedelolactone and ursolic and oleanolic acids as well asluteolin and apigenin can form the basis of new drugs against cancer arthritis gastrointestinal disorders skin diseases and liverdisorders

1 Background

Eclipta alba (L) Hassk (also known as Eclipta prostrataRoxb) belongs to the Asteraceae family and is commonlyknown as false daisy in English and bhringoraj or bhringraj inBangladesh and India It is regarded as a weed of ethnomedic-inal significance It is known in the threemajor forms of tradi-tional medicinal systems in the Indian subcontinent namelyAyurveda Unani and Siddha as bhringoraaja bhangraaand karissalaankanni respectively The Ayurvedic Pharma-copoeia of India considers the plant as hepatoprotective [1]The full taxonomic hierarchy is shown below in Table 1

Considering the ethnomedicinal significance of the plantit was of interest to review the ethnopharmacological reportson the plant and selective phytoconstituents through database searches (PubMed Scopus Google Scholar)

2 Reported Phytochemical Constituents

The plant reportedly contains a number of bioactive chemi-cals [2] The reported constituents are shown in Table 2 Thestructures of several phytoconstituents are shown in Figure 1

3 Ethnomedicinal Reports

The plant and plant parts are used fortreatment of a variety ofdiseasesby folk medicinal practitioners and tribal medicinalpractitioners of the Indian subcontinent Ethnomedicinaluses of the plant have been reported from Bangladesh IndiaNepal and Pakistan (Table 3)

The available ethnomedicinal reports indicate thatalthough there are a variety of diseases treated with theplant or plant parts the major uses are limited to treatment

Hindawi Publishing CorporationInternational Scholarly Research NoticesVolume 2014 Article ID 385969 22 pageshttpdxdoiorg1011552014385969

2 International Scholarly Research Notices

H

H

H H

H

H

H

H

HHO

HO

HOHO

HO

HO

HO

HO

HO

HO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH OH

OH

OH

OH

OH

H H

H

H

H

H

H

H

H

O

O

O

OO

O O

O O

OO

O

O

O

CH3

CH3

CH3CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3CO

120572-Amyrin

Stigmasterol Stigmasterol-3-O-glucoside

Daucosterol Wedelolactone

Demethylwedelolactone Oleanolic acid

Ursolic acid Luteolin

(a)

Figure 1 Continued

International Scholarly Research Notices 3

H

H H

H

N

HO

HO

HO

HO

HOHO

HO

OH

OH

OH

OHOH

OH

OH

OH

OH

O

HO

OH

O

O

O

O O

O

O

CH3

CH3

CH3

H3C

Luteolin-7-glucosideApigenin

Protocatechuic acid 4-Hydroxy benzoic acid Heptacosanol

Ecliptalbine

(b)

Figure 1 Structures of several phytoconstituents of E alba

Table 1 Taxonomic hierarchy of E alba

Kingdom PlantaeSubkingdom ViridaeplantaeInfrakingdom StreptophytaDivision TracheophytaSubdivision SpermatophytinaInfradivision AngiospermaeClass MagnoliopsidaSuperorder AsteranaeOrder AsteralesFamily AsteraceaeGenus Eclipta LSpecies Eclipta alba (L) Hassk

of gastrointestinal disorders respiratory tract disorders(including asthma) fever hair loss and graying of hairliver disorders (including jaundice) skin disorders spleenenlargement and cuts and wounds

4 Pharmacological Activity Reports

41 Hepatoprotective Activity The protective effect of theplant against carbon tetrachloride-induced acute liver dam-age has been reported [3] Coumestans (wedelolactone anddemethylwedelolactone) have beenmentioned as the possiblecomponents behind the protective effect on liver as well asagainst liver disorders both compounds exhibited antihepa-totoxic activity in assays employingCCl

4mdash(carbon tetrachlo-

ride) GalNmdash(galactosamine) and phalloidin-cytotoxicity inrat hepatocytes They also showed a significant stimulatoryeffect on liver cell regeneration [4] Alcoholic extract ofE alba was found to have good antihepatotoxic activity asassessed in CCl

4-induced liver damage in albino rats through

liver to body weight ratio pentobarbitone sleep time serumlevels of glutamate pyruvate transaminase (GPT) and glu-tamic oxaloacetic transaminase (GOT) alkaline phosphatase(ALP) and bilirubin In CCl

4-administered rats there was

an increase in liver weight pentobarbitone sleep time andelevated GOT GPT SALP and serum bilirubin levels Thealcoholic extract at a dose of 200mgkg significantly reversedthese effects [5]

4 International Scholarly Research Notices

Table 2 Reported phytoconstituents of E alba [2 6ndash8]

Nature ofphytoconstituent(s) Phytoconstituent(s)

Coumestan Wedelolactone demethylwedelolactone demethylwedelolactone-7-glucoside

Terpenoids and theirglycosides

Eclalbasaponins VIIndashX (taraxastane triterpene glycosides) eclalbasaponins IndashVI (oleanane triterpeneglycosides) eclalbosaponins IndashVI (triterpene glycosides) ecliptasaponins C and D (triterpenoid glucosides)120572-amyrin oleanolic acid ursolic acid (triterpenoids)

Sterol Stigmasterol daucosterol stigmasterol-3-O-glucoside

Alkaloids

[(20S)(25S)-2226-imino-cholesta-522(N)-dien-3120573-ol] (verazine)[20-epi-3-dehydroxy-3-oxo-56-dihydro-45-dehydroverazine] [(20R)-20-pyridyl-cholesta-5-ene-312057323-diol](ecliptalbine) [(20R)-4120573-hydroxyverazine] [4120573-hydroxyverazine] [(20R)-25120573-hydroxyverazine][25120573-hydroxyverazine]

Flavonoids Luteolin-7-glucoside luteolin apigenin orobol (isoluteolin)Sesquiterpenelactones

5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl agelate5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl acetate

Terthienyl aldehyde EcliptalFatty alcohols Hentriacontanol heptacosanol

Volatile oilsHeptadecane 61014-trimethyl-2-pentadecanone n-hexadecanoic acid pentadecane eudesma-4(14)11-dienephytol octadec-9-enoic ecid 12-benzenediacarboxylic acid diisooctyl ester (ZZ)-912-octadecadienoic acid(Z)-711-dimethyl-3-methylene-1610-dodecatriene (ZZZ)-1599-tetramethyl-147-cycloundecatriene

Saponins Eclalbatin (triterpene saponin) dasyscyphin CPolyacetyliniccompounds 120572-Terthienylmethanol polyacetylenes polyacetylene substituted thiophenes

Phenolic acids Protocatechuic acid 4-hydroxy benzoic acid

The hepatoprotective effect of ethanolwater (1 1) extract(Ea) of the plant has been studied inCCl

4-induced hepatotox-

icity in rats Ea significantly counteracted CCl4-induced inhi-

bition of the hepatic microsomal drug metabolising enzymeamidopyrine N-demethylase and membrane bound glucose6-phosphatase but failed to reverse the very high degreeof inhibition of another drug metabolising enzyme anilinehydroxylase The loss of hepatic lysosomal acid phosphataseand alkaline phosphatase by CCl

4was significantly restored

by Ea It was suggested that the hepatoprotective effect ofEa may be due to its regulating of the levels of hepaticmicrosomal drug metabolising enzymes [43]

The ethanolic extract of leaves of the plant has beenfractionated into three parts (hot water insoluble (EaI) ethylacetate fraction of hot water soluble (EaII) and remain-ing hot water soluble fraction (EaIII)) and each fractionstudied for hepatoprotective activity against CCl

4-induced

hepatotoxicity in rats and mice Hepatoprotective activitywas determined on the basis of their effects on parameterslike hexobarbitone sleep time zoxazolamine paralysis timebromsulfalein clearance serum transaminases (GPT GOT)and serum bilirubin All the experimental parameters wereincreased by CCl

4 fraction EaII (10ndash80mgkg po) dose-

dependently and significantly reversed these increases Frac-tion EaII was found to contain coumestan wedelolactone anddemethylwedelolactone as major components with apigeninluteolin 4-hydroxybenzoic acid and protocatechuic acid asminor constituents [44]

Hepatitis C virus (HCV) inhibitory activity has beenreported for E alba extract Phytochemical analysis of theextract revealed the presence of three compounds namely

wedelolactone luteolin and apigenin These compoundsexhibited dose-dependent inhibition of HCV replicase invitro and anti-HCV replication activity in the cell culturesystem The results suggest that the plant or individualcomponents have the potential to be used against HCV [45]

Ethanol extract of whole plant was tested for hepatopro-tective effect against paracetamol-induced hepatotoxicity inmice Treatment with 100 and 250mg of the extract per 100 kgbody weight showed significant reductions in paracetamol-induced serum alanine aminotransferase (ALT also knownas GOT) levels At the same time histopathological studiesshowed marked reductions in paracetamol-induced fattydegeneration and centrizonal necrosis in liver of extract-treated mice [46]

An alcoholic extract of freshly collected Eclipta albaexhibited dose-dependent (625ndash500mgkg po) signifi-cant hepatoprotective activity against carbon tetrachloride-induced liver injury in rats and mice as determinedthrough various tests like hexobarbitone-induced sleepzoxazolamine-induced paralysis bromsulfalein (BSP) clear-ance serum levels of transaminases bilirubin and protein[47]

A combination of ethanolic extract of E alba leavesand P longum seeds demonstrated better hepatoprotectiveaction against CCl

4-induced hepatotoxicity in rats than

either extract alone Serum marker enzymes like alanineaminotransferase (ALTGOT) aspartate aminotransferase(AST also known as GOT) acid phosphatase (AP) lac-tate dehydrogenase (LDH) 120574-glutamyl transferase (GGT)and 51015840-nucleotidase were elevated with carbon tetrachloridetreatment which were restored towards normalization by

International Scholarly Research Notices 5

Table 3 Reported ethnomedicinal uses of E alba

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Traditional practitioners of Aligarh (1)Budaun (2) Bulandshahar (3) Farrukhabad(4) Hathras (5) districts of Western UttarPradesh India [9][Reported uses in the various districts areshown in the right column in parentheses]

Acidity Plant decoction is administered thrice daily with cow milk before each meal for15 days (1ndash5)Alopecia Leaf extract is given orally twice a day for 3 months (1ndash5)Asthma Whole plant ash is given orally thrice daily for 3 months (1ndash5)Body pain Fresh leaf extract is given orally thrice daily for 5 days or till cure (1ndash5)Bronchitis and pneumonia Whole plant decoction is given orally with honey twice a dayfor 7 days or till cure (1ndash5)Burns Whole plant extract is given orally twice a day for 7 days Leaf paste is appliedexternally This is continued till cure (1ndash5)Constipation Root powder is given orally once a day for 3 days (1ndash5)Diarrhea and dysentery Whole plant decoction is given orally thrice daily for 7 days ortill cure (1ndash5)Edema Plant extract is given twice a day for 7 days or till cureFever Whole plant extract is given orally twice or thrice daily for 7 days or till cure (1ndash5)General weakness Whole plant extract mixed with 3 g fruit powder of Phyllanthusemblica is given orally twice a day for 6 weeks or till the person recovers from weakness(1ndash5)Gingivitis Leaf extract is given orally twice a day for 3 weeks or till cure (1ndash5)Hemorrhoids Root extract is administered orally thrice daily (1 2)Hair fall Leaf extract is given orally twice daily with cow milk for 3 months (1ndash5)High blood pressure Plant decoction is given orally twice or thrice a day for 3 months ortill the patient recovers fully (1ndash5)Jaundice Fresh plant extract is given orally twice or thrice daily for 3 weeks or till cureLeaf extract along with honey is given orally twice or thrice daily for 15 days or till curePlant extract mixed with plant extract of Boerhavia diffusa is given orally twice a day for15 days or till cure (1 2)Liver enlargement Plant extract is given orally twice or thrice daily for 1 month or tillcure This therapy is administered to adult patients only (1ndash5)Loss of appetite Leaf decoction is given orally before each meal twice daily for 15 daysLeaf powder is given orally after each meal for 15 days (1 2 6)Palpitation of heart Leaf extract mixed with honey is given orally twice a day for 7 daysor till cure (1ndash5)Paronychia or whitlo Whole plant paste is applied externally (1ndash5)Pimples Fresh leaf extract is given orally twice daily with cow milk for 2 months (1ndash5)Premature graying of hair Fresh leaf extract is gently applied to hair (1ndash5)Skin diseases Plant paste is applied externally for 15 days in eczema Leaf paste is appliedexternally to boils and extract is given orally twice daily for 15 days (1 2 5)Spleen enlargement Leaf extract mixed with honey is given orally twice or thrice dailyfor 15 days or till cureUrinary tract infections Plant extract is given orally twice a day for 15 days The extract isalso used to wash genitalia externally till cure (1ndash5)Weakness of vision Leaf extract is given orally twice a day with cow milk for 3 months(1ndash3)Wounds Leaf extract is used to wash open wounds (1 3 5)Wrinkles Leaf extract withWithania somnifera root powder is given orally with cowmilk twice daily for 3 months (1ndash5)

Local practitioners of Mount Abu inRajasthan India [10]

Leaves and flowers used for treatment of urinary problems jaundice asthma andcoughs

Local community of Jalalpur Jattan Gujratdistrict Punjab Pakistan [11] Leaf paste applied to treat allergy atheletersquos foot and ringworm

Santal tribe residing inThakurgaon districtBangladesh [12]

Diabetes Leaves of white-flowered plant are mixed with leaves of Scoparia dulcis leavesof Cynodon dactylon and water and then boiled in an earthen vessel The water is thenstrained through cloth and given to diabetic patients to be taken orally in the morningand evening on an empty stomach

Inhabitants of Mansoora Malegaon India[13]

Plant is used as tonic deobstruent emetic and considered useful in enlargement of liverand spleen

Chakma tribe of Tripura State India [14] Two teaspoons of leaf juice is administered daily against hepatic disorders

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

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AntibioticsInternational Journal of

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StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

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AddictionJournal of

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BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

2 International Scholarly Research Notices

H

H

H H

H

H

H

H

HHO

HO

HOHO

HO

HO

HO

HO

HO

HO

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH OH

OH

OH

OH

OH

H H

H

H

H

H

H

H

H

O

O

O

OO

O O

O O

OO

O

O

O

CH3

CH3

CH3CH3

CH3CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

CH3

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3C

H3CO

120572-Amyrin

Stigmasterol Stigmasterol-3-O-glucoside

Daucosterol Wedelolactone

Demethylwedelolactone Oleanolic acid

Ursolic acid Luteolin

(a)

Figure 1 Continued

International Scholarly Research Notices 3

H

H H

H

N

HO

HO

HO

HO

HOHO

HO

OH

OH

OH

OHOH

OH

OH

OH

OH

O

HO

OH

O

O

O

O O

O

O

CH3

CH3

CH3

H3C

Luteolin-7-glucosideApigenin

Protocatechuic acid 4-Hydroxy benzoic acid Heptacosanol

Ecliptalbine

(b)

Figure 1 Structures of several phytoconstituents of E alba

Table 1 Taxonomic hierarchy of E alba

Kingdom PlantaeSubkingdom ViridaeplantaeInfrakingdom StreptophytaDivision TracheophytaSubdivision SpermatophytinaInfradivision AngiospermaeClass MagnoliopsidaSuperorder AsteranaeOrder AsteralesFamily AsteraceaeGenus Eclipta LSpecies Eclipta alba (L) Hassk

of gastrointestinal disorders respiratory tract disorders(including asthma) fever hair loss and graying of hairliver disorders (including jaundice) skin disorders spleenenlargement and cuts and wounds

4 Pharmacological Activity Reports

41 Hepatoprotective Activity The protective effect of theplant against carbon tetrachloride-induced acute liver dam-age has been reported [3] Coumestans (wedelolactone anddemethylwedelolactone) have beenmentioned as the possiblecomponents behind the protective effect on liver as well asagainst liver disorders both compounds exhibited antihepa-totoxic activity in assays employingCCl

4mdash(carbon tetrachlo-

ride) GalNmdash(galactosamine) and phalloidin-cytotoxicity inrat hepatocytes They also showed a significant stimulatoryeffect on liver cell regeneration [4] Alcoholic extract ofE alba was found to have good antihepatotoxic activity asassessed in CCl

4-induced liver damage in albino rats through

liver to body weight ratio pentobarbitone sleep time serumlevels of glutamate pyruvate transaminase (GPT) and glu-tamic oxaloacetic transaminase (GOT) alkaline phosphatase(ALP) and bilirubin In CCl

4-administered rats there was

an increase in liver weight pentobarbitone sleep time andelevated GOT GPT SALP and serum bilirubin levels Thealcoholic extract at a dose of 200mgkg significantly reversedthese effects [5]

4 International Scholarly Research Notices

Table 2 Reported phytoconstituents of E alba [2 6ndash8]

Nature ofphytoconstituent(s) Phytoconstituent(s)

Coumestan Wedelolactone demethylwedelolactone demethylwedelolactone-7-glucoside

Terpenoids and theirglycosides

Eclalbasaponins VIIndashX (taraxastane triterpene glycosides) eclalbasaponins IndashVI (oleanane triterpeneglycosides) eclalbosaponins IndashVI (triterpene glycosides) ecliptasaponins C and D (triterpenoid glucosides)120572-amyrin oleanolic acid ursolic acid (triterpenoids)

Sterol Stigmasterol daucosterol stigmasterol-3-O-glucoside

Alkaloids

[(20S)(25S)-2226-imino-cholesta-522(N)-dien-3120573-ol] (verazine)[20-epi-3-dehydroxy-3-oxo-56-dihydro-45-dehydroverazine] [(20R)-20-pyridyl-cholesta-5-ene-312057323-diol](ecliptalbine) [(20R)-4120573-hydroxyverazine] [4120573-hydroxyverazine] [(20R)-25120573-hydroxyverazine][25120573-hydroxyverazine]

Flavonoids Luteolin-7-glucoside luteolin apigenin orobol (isoluteolin)Sesquiterpenelactones

5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl agelate5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl acetate

Terthienyl aldehyde EcliptalFatty alcohols Hentriacontanol heptacosanol

Volatile oilsHeptadecane 61014-trimethyl-2-pentadecanone n-hexadecanoic acid pentadecane eudesma-4(14)11-dienephytol octadec-9-enoic ecid 12-benzenediacarboxylic acid diisooctyl ester (ZZ)-912-octadecadienoic acid(Z)-711-dimethyl-3-methylene-1610-dodecatriene (ZZZ)-1599-tetramethyl-147-cycloundecatriene

Saponins Eclalbatin (triterpene saponin) dasyscyphin CPolyacetyliniccompounds 120572-Terthienylmethanol polyacetylenes polyacetylene substituted thiophenes

Phenolic acids Protocatechuic acid 4-hydroxy benzoic acid

The hepatoprotective effect of ethanolwater (1 1) extract(Ea) of the plant has been studied inCCl

4-induced hepatotox-

icity in rats Ea significantly counteracted CCl4-induced inhi-

bition of the hepatic microsomal drug metabolising enzymeamidopyrine N-demethylase and membrane bound glucose6-phosphatase but failed to reverse the very high degreeof inhibition of another drug metabolising enzyme anilinehydroxylase The loss of hepatic lysosomal acid phosphataseand alkaline phosphatase by CCl

4was significantly restored

by Ea It was suggested that the hepatoprotective effect ofEa may be due to its regulating of the levels of hepaticmicrosomal drug metabolising enzymes [43]

The ethanolic extract of leaves of the plant has beenfractionated into three parts (hot water insoluble (EaI) ethylacetate fraction of hot water soluble (EaII) and remain-ing hot water soluble fraction (EaIII)) and each fractionstudied for hepatoprotective activity against CCl

4-induced

hepatotoxicity in rats and mice Hepatoprotective activitywas determined on the basis of their effects on parameterslike hexobarbitone sleep time zoxazolamine paralysis timebromsulfalein clearance serum transaminases (GPT GOT)and serum bilirubin All the experimental parameters wereincreased by CCl

4 fraction EaII (10ndash80mgkg po) dose-

dependently and significantly reversed these increases Frac-tion EaII was found to contain coumestan wedelolactone anddemethylwedelolactone as major components with apigeninluteolin 4-hydroxybenzoic acid and protocatechuic acid asminor constituents [44]

Hepatitis C virus (HCV) inhibitory activity has beenreported for E alba extract Phytochemical analysis of theextract revealed the presence of three compounds namely

wedelolactone luteolin and apigenin These compoundsexhibited dose-dependent inhibition of HCV replicase invitro and anti-HCV replication activity in the cell culturesystem The results suggest that the plant or individualcomponents have the potential to be used against HCV [45]

Ethanol extract of whole plant was tested for hepatopro-tective effect against paracetamol-induced hepatotoxicity inmice Treatment with 100 and 250mg of the extract per 100 kgbody weight showed significant reductions in paracetamol-induced serum alanine aminotransferase (ALT also knownas GOT) levels At the same time histopathological studiesshowed marked reductions in paracetamol-induced fattydegeneration and centrizonal necrosis in liver of extract-treated mice [46]

An alcoholic extract of freshly collected Eclipta albaexhibited dose-dependent (625ndash500mgkg po) signifi-cant hepatoprotective activity against carbon tetrachloride-induced liver injury in rats and mice as determinedthrough various tests like hexobarbitone-induced sleepzoxazolamine-induced paralysis bromsulfalein (BSP) clear-ance serum levels of transaminases bilirubin and protein[47]

A combination of ethanolic extract of E alba leavesand P longum seeds demonstrated better hepatoprotectiveaction against CCl

4-induced hepatotoxicity in rats than

either extract alone Serum marker enzymes like alanineaminotransferase (ALTGOT) aspartate aminotransferase(AST also known as GOT) acid phosphatase (AP) lac-tate dehydrogenase (LDH) 120574-glutamyl transferase (GGT)and 51015840-nucleotidase were elevated with carbon tetrachloridetreatment which were restored towards normalization by

International Scholarly Research Notices 5

Table 3 Reported ethnomedicinal uses of E alba

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Traditional practitioners of Aligarh (1)Budaun (2) Bulandshahar (3) Farrukhabad(4) Hathras (5) districts of Western UttarPradesh India [9][Reported uses in the various districts areshown in the right column in parentheses]

Acidity Plant decoction is administered thrice daily with cow milk before each meal for15 days (1ndash5)Alopecia Leaf extract is given orally twice a day for 3 months (1ndash5)Asthma Whole plant ash is given orally thrice daily for 3 months (1ndash5)Body pain Fresh leaf extract is given orally thrice daily for 5 days or till cure (1ndash5)Bronchitis and pneumonia Whole plant decoction is given orally with honey twice a dayfor 7 days or till cure (1ndash5)Burns Whole plant extract is given orally twice a day for 7 days Leaf paste is appliedexternally This is continued till cure (1ndash5)Constipation Root powder is given orally once a day for 3 days (1ndash5)Diarrhea and dysentery Whole plant decoction is given orally thrice daily for 7 days ortill cure (1ndash5)Edema Plant extract is given twice a day for 7 days or till cureFever Whole plant extract is given orally twice or thrice daily for 7 days or till cure (1ndash5)General weakness Whole plant extract mixed with 3 g fruit powder of Phyllanthusemblica is given orally twice a day for 6 weeks or till the person recovers from weakness(1ndash5)Gingivitis Leaf extract is given orally twice a day for 3 weeks or till cure (1ndash5)Hemorrhoids Root extract is administered orally thrice daily (1 2)Hair fall Leaf extract is given orally twice daily with cow milk for 3 months (1ndash5)High blood pressure Plant decoction is given orally twice or thrice a day for 3 months ortill the patient recovers fully (1ndash5)Jaundice Fresh plant extract is given orally twice or thrice daily for 3 weeks or till cureLeaf extract along with honey is given orally twice or thrice daily for 15 days or till curePlant extract mixed with plant extract of Boerhavia diffusa is given orally twice a day for15 days or till cure (1 2)Liver enlargement Plant extract is given orally twice or thrice daily for 1 month or tillcure This therapy is administered to adult patients only (1ndash5)Loss of appetite Leaf decoction is given orally before each meal twice daily for 15 daysLeaf powder is given orally after each meal for 15 days (1 2 6)Palpitation of heart Leaf extract mixed with honey is given orally twice a day for 7 daysor till cure (1ndash5)Paronychia or whitlo Whole plant paste is applied externally (1ndash5)Pimples Fresh leaf extract is given orally twice daily with cow milk for 2 months (1ndash5)Premature graying of hair Fresh leaf extract is gently applied to hair (1ndash5)Skin diseases Plant paste is applied externally for 15 days in eczema Leaf paste is appliedexternally to boils and extract is given orally twice daily for 15 days (1 2 5)Spleen enlargement Leaf extract mixed with honey is given orally twice or thrice dailyfor 15 days or till cureUrinary tract infections Plant extract is given orally twice a day for 15 days The extract isalso used to wash genitalia externally till cure (1ndash5)Weakness of vision Leaf extract is given orally twice a day with cow milk for 3 months(1ndash3)Wounds Leaf extract is used to wash open wounds (1 3 5)Wrinkles Leaf extract withWithania somnifera root powder is given orally with cowmilk twice daily for 3 months (1ndash5)

Local practitioners of Mount Abu inRajasthan India [10]

Leaves and flowers used for treatment of urinary problems jaundice asthma andcoughs

Local community of Jalalpur Jattan Gujratdistrict Punjab Pakistan [11] Leaf paste applied to treat allergy atheletersquos foot and ringworm

Santal tribe residing inThakurgaon districtBangladesh [12]

Diabetes Leaves of white-flowered plant are mixed with leaves of Scoparia dulcis leavesof Cynodon dactylon and water and then boiled in an earthen vessel The water is thenstrained through cloth and given to diabetic patients to be taken orally in the morningand evening on an empty stomach

Inhabitants of Mansoora Malegaon India[13]

Plant is used as tonic deobstruent emetic and considered useful in enlargement of liverand spleen

Chakma tribe of Tripura State India [14] Two teaspoons of leaf juice is administered daily against hepatic disorders

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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Volume 2014

ToxinsJournal of

VaccinesJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 3

H

H H

H

N

HO

HO

HO

HO

HOHO

HO

OH

OH

OH

OHOH

OH

OH

OH

OH

O

HO

OH

O

O

O

O O

O

O

CH3

CH3

CH3

H3C

Luteolin-7-glucosideApigenin

Protocatechuic acid 4-Hydroxy benzoic acid Heptacosanol

Ecliptalbine

(b)

Figure 1 Structures of several phytoconstituents of E alba

Table 1 Taxonomic hierarchy of E alba

Kingdom PlantaeSubkingdom ViridaeplantaeInfrakingdom StreptophytaDivision TracheophytaSubdivision SpermatophytinaInfradivision AngiospermaeClass MagnoliopsidaSuperorder AsteranaeOrder AsteralesFamily AsteraceaeGenus Eclipta LSpecies Eclipta alba (L) Hassk

of gastrointestinal disorders respiratory tract disorders(including asthma) fever hair loss and graying of hairliver disorders (including jaundice) skin disorders spleenenlargement and cuts and wounds

4 Pharmacological Activity Reports

41 Hepatoprotective Activity The protective effect of theplant against carbon tetrachloride-induced acute liver dam-age has been reported [3] Coumestans (wedelolactone anddemethylwedelolactone) have beenmentioned as the possiblecomponents behind the protective effect on liver as well asagainst liver disorders both compounds exhibited antihepa-totoxic activity in assays employingCCl

4mdash(carbon tetrachlo-

ride) GalNmdash(galactosamine) and phalloidin-cytotoxicity inrat hepatocytes They also showed a significant stimulatoryeffect on liver cell regeneration [4] Alcoholic extract ofE alba was found to have good antihepatotoxic activity asassessed in CCl

4-induced liver damage in albino rats through

liver to body weight ratio pentobarbitone sleep time serumlevels of glutamate pyruvate transaminase (GPT) and glu-tamic oxaloacetic transaminase (GOT) alkaline phosphatase(ALP) and bilirubin In CCl

4-administered rats there was

an increase in liver weight pentobarbitone sleep time andelevated GOT GPT SALP and serum bilirubin levels Thealcoholic extract at a dose of 200mgkg significantly reversedthese effects [5]

4 International Scholarly Research Notices

Table 2 Reported phytoconstituents of E alba [2 6ndash8]

Nature ofphytoconstituent(s) Phytoconstituent(s)

Coumestan Wedelolactone demethylwedelolactone demethylwedelolactone-7-glucoside

Terpenoids and theirglycosides

Eclalbasaponins VIIndashX (taraxastane triterpene glycosides) eclalbasaponins IndashVI (oleanane triterpeneglycosides) eclalbosaponins IndashVI (triterpene glycosides) ecliptasaponins C and D (triterpenoid glucosides)120572-amyrin oleanolic acid ursolic acid (triterpenoids)

Sterol Stigmasterol daucosterol stigmasterol-3-O-glucoside

Alkaloids

[(20S)(25S)-2226-imino-cholesta-522(N)-dien-3120573-ol] (verazine)[20-epi-3-dehydroxy-3-oxo-56-dihydro-45-dehydroverazine] [(20R)-20-pyridyl-cholesta-5-ene-312057323-diol](ecliptalbine) [(20R)-4120573-hydroxyverazine] [4120573-hydroxyverazine] [(20R)-25120573-hydroxyverazine][25120573-hydroxyverazine]

Flavonoids Luteolin-7-glucoside luteolin apigenin orobol (isoluteolin)Sesquiterpenelactones

5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl agelate5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl acetate

Terthienyl aldehyde EcliptalFatty alcohols Hentriacontanol heptacosanol

Volatile oilsHeptadecane 61014-trimethyl-2-pentadecanone n-hexadecanoic acid pentadecane eudesma-4(14)11-dienephytol octadec-9-enoic ecid 12-benzenediacarboxylic acid diisooctyl ester (ZZ)-912-octadecadienoic acid(Z)-711-dimethyl-3-methylene-1610-dodecatriene (ZZZ)-1599-tetramethyl-147-cycloundecatriene

Saponins Eclalbatin (triterpene saponin) dasyscyphin CPolyacetyliniccompounds 120572-Terthienylmethanol polyacetylenes polyacetylene substituted thiophenes

Phenolic acids Protocatechuic acid 4-hydroxy benzoic acid

The hepatoprotective effect of ethanolwater (1 1) extract(Ea) of the plant has been studied inCCl

4-induced hepatotox-

icity in rats Ea significantly counteracted CCl4-induced inhi-

bition of the hepatic microsomal drug metabolising enzymeamidopyrine N-demethylase and membrane bound glucose6-phosphatase but failed to reverse the very high degreeof inhibition of another drug metabolising enzyme anilinehydroxylase The loss of hepatic lysosomal acid phosphataseand alkaline phosphatase by CCl

4was significantly restored

by Ea It was suggested that the hepatoprotective effect ofEa may be due to its regulating of the levels of hepaticmicrosomal drug metabolising enzymes [43]

The ethanolic extract of leaves of the plant has beenfractionated into three parts (hot water insoluble (EaI) ethylacetate fraction of hot water soluble (EaII) and remain-ing hot water soluble fraction (EaIII)) and each fractionstudied for hepatoprotective activity against CCl

4-induced

hepatotoxicity in rats and mice Hepatoprotective activitywas determined on the basis of their effects on parameterslike hexobarbitone sleep time zoxazolamine paralysis timebromsulfalein clearance serum transaminases (GPT GOT)and serum bilirubin All the experimental parameters wereincreased by CCl

4 fraction EaII (10ndash80mgkg po) dose-

dependently and significantly reversed these increases Frac-tion EaII was found to contain coumestan wedelolactone anddemethylwedelolactone as major components with apigeninluteolin 4-hydroxybenzoic acid and protocatechuic acid asminor constituents [44]

Hepatitis C virus (HCV) inhibitory activity has beenreported for E alba extract Phytochemical analysis of theextract revealed the presence of three compounds namely

wedelolactone luteolin and apigenin These compoundsexhibited dose-dependent inhibition of HCV replicase invitro and anti-HCV replication activity in the cell culturesystem The results suggest that the plant or individualcomponents have the potential to be used against HCV [45]

Ethanol extract of whole plant was tested for hepatopro-tective effect against paracetamol-induced hepatotoxicity inmice Treatment with 100 and 250mg of the extract per 100 kgbody weight showed significant reductions in paracetamol-induced serum alanine aminotransferase (ALT also knownas GOT) levels At the same time histopathological studiesshowed marked reductions in paracetamol-induced fattydegeneration and centrizonal necrosis in liver of extract-treated mice [46]

An alcoholic extract of freshly collected Eclipta albaexhibited dose-dependent (625ndash500mgkg po) signifi-cant hepatoprotective activity against carbon tetrachloride-induced liver injury in rats and mice as determinedthrough various tests like hexobarbitone-induced sleepzoxazolamine-induced paralysis bromsulfalein (BSP) clear-ance serum levels of transaminases bilirubin and protein[47]

A combination of ethanolic extract of E alba leavesand P longum seeds demonstrated better hepatoprotectiveaction against CCl

4-induced hepatotoxicity in rats than

either extract alone Serum marker enzymes like alanineaminotransferase (ALTGOT) aspartate aminotransferase(AST also known as GOT) acid phosphatase (AP) lac-tate dehydrogenase (LDH) 120574-glutamyl transferase (GGT)and 51015840-nucleotidase were elevated with carbon tetrachloridetreatment which were restored towards normalization by

International Scholarly Research Notices 5

Table 3 Reported ethnomedicinal uses of E alba

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Traditional practitioners of Aligarh (1)Budaun (2) Bulandshahar (3) Farrukhabad(4) Hathras (5) districts of Western UttarPradesh India [9][Reported uses in the various districts areshown in the right column in parentheses]

Acidity Plant decoction is administered thrice daily with cow milk before each meal for15 days (1ndash5)Alopecia Leaf extract is given orally twice a day for 3 months (1ndash5)Asthma Whole plant ash is given orally thrice daily for 3 months (1ndash5)Body pain Fresh leaf extract is given orally thrice daily for 5 days or till cure (1ndash5)Bronchitis and pneumonia Whole plant decoction is given orally with honey twice a dayfor 7 days or till cure (1ndash5)Burns Whole plant extract is given orally twice a day for 7 days Leaf paste is appliedexternally This is continued till cure (1ndash5)Constipation Root powder is given orally once a day for 3 days (1ndash5)Diarrhea and dysentery Whole plant decoction is given orally thrice daily for 7 days ortill cure (1ndash5)Edema Plant extract is given twice a day for 7 days or till cureFever Whole plant extract is given orally twice or thrice daily for 7 days or till cure (1ndash5)General weakness Whole plant extract mixed with 3 g fruit powder of Phyllanthusemblica is given orally twice a day for 6 weeks or till the person recovers from weakness(1ndash5)Gingivitis Leaf extract is given orally twice a day for 3 weeks or till cure (1ndash5)Hemorrhoids Root extract is administered orally thrice daily (1 2)Hair fall Leaf extract is given orally twice daily with cow milk for 3 months (1ndash5)High blood pressure Plant decoction is given orally twice or thrice a day for 3 months ortill the patient recovers fully (1ndash5)Jaundice Fresh plant extract is given orally twice or thrice daily for 3 weeks or till cureLeaf extract along with honey is given orally twice or thrice daily for 15 days or till curePlant extract mixed with plant extract of Boerhavia diffusa is given orally twice a day for15 days or till cure (1 2)Liver enlargement Plant extract is given orally twice or thrice daily for 1 month or tillcure This therapy is administered to adult patients only (1ndash5)Loss of appetite Leaf decoction is given orally before each meal twice daily for 15 daysLeaf powder is given orally after each meal for 15 days (1 2 6)Palpitation of heart Leaf extract mixed with honey is given orally twice a day for 7 daysor till cure (1ndash5)Paronychia or whitlo Whole plant paste is applied externally (1ndash5)Pimples Fresh leaf extract is given orally twice daily with cow milk for 2 months (1ndash5)Premature graying of hair Fresh leaf extract is gently applied to hair (1ndash5)Skin diseases Plant paste is applied externally for 15 days in eczema Leaf paste is appliedexternally to boils and extract is given orally twice daily for 15 days (1 2 5)Spleen enlargement Leaf extract mixed with honey is given orally twice or thrice dailyfor 15 days or till cureUrinary tract infections Plant extract is given orally twice a day for 15 days The extract isalso used to wash genitalia externally till cure (1ndash5)Weakness of vision Leaf extract is given orally twice a day with cow milk for 3 months(1ndash3)Wounds Leaf extract is used to wash open wounds (1 3 5)Wrinkles Leaf extract withWithania somnifera root powder is given orally with cowmilk twice daily for 3 months (1ndash5)

Local practitioners of Mount Abu inRajasthan India [10]

Leaves and flowers used for treatment of urinary problems jaundice asthma andcoughs

Local community of Jalalpur Jattan Gujratdistrict Punjab Pakistan [11] Leaf paste applied to treat allergy atheletersquos foot and ringworm

Santal tribe residing inThakurgaon districtBangladesh [12]

Diabetes Leaves of white-flowered plant are mixed with leaves of Scoparia dulcis leavesof Cynodon dactylon and water and then boiled in an earthen vessel The water is thenstrained through cloth and given to diabetic patients to be taken orally in the morningand evening on an empty stomach

Inhabitants of Mansoora Malegaon India[13]

Plant is used as tonic deobstruent emetic and considered useful in enlargement of liverand spleen

Chakma tribe of Tripura State India [14] Two teaspoons of leaf juice is administered daily against hepatic disorders

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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Hindawi Publishing Corporationhttpwwwhindawicom

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ToxinsJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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MEDIATORSINFLAMMATION

of

4 International Scholarly Research Notices

Table 2 Reported phytoconstituents of E alba [2 6ndash8]

Nature ofphytoconstituent(s) Phytoconstituent(s)

Coumestan Wedelolactone demethylwedelolactone demethylwedelolactone-7-glucoside

Terpenoids and theirglycosides

Eclalbasaponins VIIndashX (taraxastane triterpene glycosides) eclalbasaponins IndashVI (oleanane triterpeneglycosides) eclalbosaponins IndashVI (triterpene glycosides) ecliptasaponins C and D (triterpenoid glucosides)120572-amyrin oleanolic acid ursolic acid (triterpenoids)

Sterol Stigmasterol daucosterol stigmasterol-3-O-glucoside

Alkaloids

[(20S)(25S)-2226-imino-cholesta-522(N)-dien-3120573-ol] (verazine)[20-epi-3-dehydroxy-3-oxo-56-dihydro-45-dehydroverazine] [(20R)-20-pyridyl-cholesta-5-ene-312057323-diol](ecliptalbine) [(20R)-4120573-hydroxyverazine] [4120573-hydroxyverazine] [(20R)-25120573-hydroxyverazine][25120573-hydroxyverazine]

Flavonoids Luteolin-7-glucoside luteolin apigenin orobol (isoluteolin)Sesquiterpenelactones

5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl agelate5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl acetate

Terthienyl aldehyde EcliptalFatty alcohols Hentriacontanol heptacosanol

Volatile oilsHeptadecane 61014-trimethyl-2-pentadecanone n-hexadecanoic acid pentadecane eudesma-4(14)11-dienephytol octadec-9-enoic ecid 12-benzenediacarboxylic acid diisooctyl ester (ZZ)-912-octadecadienoic acid(Z)-711-dimethyl-3-methylene-1610-dodecatriene (ZZZ)-1599-tetramethyl-147-cycloundecatriene

Saponins Eclalbatin (triterpene saponin) dasyscyphin CPolyacetyliniccompounds 120572-Terthienylmethanol polyacetylenes polyacetylene substituted thiophenes

Phenolic acids Protocatechuic acid 4-hydroxy benzoic acid

The hepatoprotective effect of ethanolwater (1 1) extract(Ea) of the plant has been studied inCCl

4-induced hepatotox-

icity in rats Ea significantly counteracted CCl4-induced inhi-

bition of the hepatic microsomal drug metabolising enzymeamidopyrine N-demethylase and membrane bound glucose6-phosphatase but failed to reverse the very high degreeof inhibition of another drug metabolising enzyme anilinehydroxylase The loss of hepatic lysosomal acid phosphataseand alkaline phosphatase by CCl

4was significantly restored

by Ea It was suggested that the hepatoprotective effect ofEa may be due to its regulating of the levels of hepaticmicrosomal drug metabolising enzymes [43]

The ethanolic extract of leaves of the plant has beenfractionated into three parts (hot water insoluble (EaI) ethylacetate fraction of hot water soluble (EaII) and remain-ing hot water soluble fraction (EaIII)) and each fractionstudied for hepatoprotective activity against CCl

4-induced

hepatotoxicity in rats and mice Hepatoprotective activitywas determined on the basis of their effects on parameterslike hexobarbitone sleep time zoxazolamine paralysis timebromsulfalein clearance serum transaminases (GPT GOT)and serum bilirubin All the experimental parameters wereincreased by CCl

4 fraction EaII (10ndash80mgkg po) dose-

dependently and significantly reversed these increases Frac-tion EaII was found to contain coumestan wedelolactone anddemethylwedelolactone as major components with apigeninluteolin 4-hydroxybenzoic acid and protocatechuic acid asminor constituents [44]

Hepatitis C virus (HCV) inhibitory activity has beenreported for E alba extract Phytochemical analysis of theextract revealed the presence of three compounds namely

wedelolactone luteolin and apigenin These compoundsexhibited dose-dependent inhibition of HCV replicase invitro and anti-HCV replication activity in the cell culturesystem The results suggest that the plant or individualcomponents have the potential to be used against HCV [45]

Ethanol extract of whole plant was tested for hepatopro-tective effect against paracetamol-induced hepatotoxicity inmice Treatment with 100 and 250mg of the extract per 100 kgbody weight showed significant reductions in paracetamol-induced serum alanine aminotransferase (ALT also knownas GOT) levels At the same time histopathological studiesshowed marked reductions in paracetamol-induced fattydegeneration and centrizonal necrosis in liver of extract-treated mice [46]

An alcoholic extract of freshly collected Eclipta albaexhibited dose-dependent (625ndash500mgkg po) signifi-cant hepatoprotective activity against carbon tetrachloride-induced liver injury in rats and mice as determinedthrough various tests like hexobarbitone-induced sleepzoxazolamine-induced paralysis bromsulfalein (BSP) clear-ance serum levels of transaminases bilirubin and protein[47]

A combination of ethanolic extract of E alba leavesand P longum seeds demonstrated better hepatoprotectiveaction against CCl

4-induced hepatotoxicity in rats than

either extract alone Serum marker enzymes like alanineaminotransferase (ALTGOT) aspartate aminotransferase(AST also known as GOT) acid phosphatase (AP) lac-tate dehydrogenase (LDH) 120574-glutamyl transferase (GGT)and 51015840-nucleotidase were elevated with carbon tetrachloridetreatment which were restored towards normalization by

International Scholarly Research Notices 5

Table 3 Reported ethnomedicinal uses of E alba

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Traditional practitioners of Aligarh (1)Budaun (2) Bulandshahar (3) Farrukhabad(4) Hathras (5) districts of Western UttarPradesh India [9][Reported uses in the various districts areshown in the right column in parentheses]

Acidity Plant decoction is administered thrice daily with cow milk before each meal for15 days (1ndash5)Alopecia Leaf extract is given orally twice a day for 3 months (1ndash5)Asthma Whole plant ash is given orally thrice daily for 3 months (1ndash5)Body pain Fresh leaf extract is given orally thrice daily for 5 days or till cure (1ndash5)Bronchitis and pneumonia Whole plant decoction is given orally with honey twice a dayfor 7 days or till cure (1ndash5)Burns Whole plant extract is given orally twice a day for 7 days Leaf paste is appliedexternally This is continued till cure (1ndash5)Constipation Root powder is given orally once a day for 3 days (1ndash5)Diarrhea and dysentery Whole plant decoction is given orally thrice daily for 7 days ortill cure (1ndash5)Edema Plant extract is given twice a day for 7 days or till cureFever Whole plant extract is given orally twice or thrice daily for 7 days or till cure (1ndash5)General weakness Whole plant extract mixed with 3 g fruit powder of Phyllanthusemblica is given orally twice a day for 6 weeks or till the person recovers from weakness(1ndash5)Gingivitis Leaf extract is given orally twice a day for 3 weeks or till cure (1ndash5)Hemorrhoids Root extract is administered orally thrice daily (1 2)Hair fall Leaf extract is given orally twice daily with cow milk for 3 months (1ndash5)High blood pressure Plant decoction is given orally twice or thrice a day for 3 months ortill the patient recovers fully (1ndash5)Jaundice Fresh plant extract is given orally twice or thrice daily for 3 weeks or till cureLeaf extract along with honey is given orally twice or thrice daily for 15 days or till curePlant extract mixed with plant extract of Boerhavia diffusa is given orally twice a day for15 days or till cure (1 2)Liver enlargement Plant extract is given orally twice or thrice daily for 1 month or tillcure This therapy is administered to adult patients only (1ndash5)Loss of appetite Leaf decoction is given orally before each meal twice daily for 15 daysLeaf powder is given orally after each meal for 15 days (1 2 6)Palpitation of heart Leaf extract mixed with honey is given orally twice a day for 7 daysor till cure (1ndash5)Paronychia or whitlo Whole plant paste is applied externally (1ndash5)Pimples Fresh leaf extract is given orally twice daily with cow milk for 2 months (1ndash5)Premature graying of hair Fresh leaf extract is gently applied to hair (1ndash5)Skin diseases Plant paste is applied externally for 15 days in eczema Leaf paste is appliedexternally to boils and extract is given orally twice daily for 15 days (1 2 5)Spleen enlargement Leaf extract mixed with honey is given orally twice or thrice dailyfor 15 days or till cureUrinary tract infections Plant extract is given orally twice a day for 15 days The extract isalso used to wash genitalia externally till cure (1ndash5)Weakness of vision Leaf extract is given orally twice a day with cow milk for 3 months(1ndash3)Wounds Leaf extract is used to wash open wounds (1 3 5)Wrinkles Leaf extract withWithania somnifera root powder is given orally with cowmilk twice daily for 3 months (1ndash5)

Local practitioners of Mount Abu inRajasthan India [10]

Leaves and flowers used for treatment of urinary problems jaundice asthma andcoughs

Local community of Jalalpur Jattan Gujratdistrict Punjab Pakistan [11] Leaf paste applied to treat allergy atheletersquos foot and ringworm

Santal tribe residing inThakurgaon districtBangladesh [12]

Diabetes Leaves of white-flowered plant are mixed with leaves of Scoparia dulcis leavesof Cynodon dactylon and water and then boiled in an earthen vessel The water is thenstrained through cloth and given to diabetic patients to be taken orally in the morningand evening on an empty stomach

Inhabitants of Mansoora Malegaon India[13]

Plant is used as tonic deobstruent emetic and considered useful in enlargement of liverand spleen

Chakma tribe of Tripura State India [14] Two teaspoons of leaf juice is administered daily against hepatic disorders

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

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International Scholarly Research Notices 5

Table 3 Reported ethnomedicinal uses of E alba

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Traditional practitioners of Aligarh (1)Budaun (2) Bulandshahar (3) Farrukhabad(4) Hathras (5) districts of Western UttarPradesh India [9][Reported uses in the various districts areshown in the right column in parentheses]

Acidity Plant decoction is administered thrice daily with cow milk before each meal for15 days (1ndash5)Alopecia Leaf extract is given orally twice a day for 3 months (1ndash5)Asthma Whole plant ash is given orally thrice daily for 3 months (1ndash5)Body pain Fresh leaf extract is given orally thrice daily for 5 days or till cure (1ndash5)Bronchitis and pneumonia Whole plant decoction is given orally with honey twice a dayfor 7 days or till cure (1ndash5)Burns Whole plant extract is given orally twice a day for 7 days Leaf paste is appliedexternally This is continued till cure (1ndash5)Constipation Root powder is given orally once a day for 3 days (1ndash5)Diarrhea and dysentery Whole plant decoction is given orally thrice daily for 7 days ortill cure (1ndash5)Edema Plant extract is given twice a day for 7 days or till cureFever Whole plant extract is given orally twice or thrice daily for 7 days or till cure (1ndash5)General weakness Whole plant extract mixed with 3 g fruit powder of Phyllanthusemblica is given orally twice a day for 6 weeks or till the person recovers from weakness(1ndash5)Gingivitis Leaf extract is given orally twice a day for 3 weeks or till cure (1ndash5)Hemorrhoids Root extract is administered orally thrice daily (1 2)Hair fall Leaf extract is given orally twice daily with cow milk for 3 months (1ndash5)High blood pressure Plant decoction is given orally twice or thrice a day for 3 months ortill the patient recovers fully (1ndash5)Jaundice Fresh plant extract is given orally twice or thrice daily for 3 weeks or till cureLeaf extract along with honey is given orally twice or thrice daily for 15 days or till curePlant extract mixed with plant extract of Boerhavia diffusa is given orally twice a day for15 days or till cure (1 2)Liver enlargement Plant extract is given orally twice or thrice daily for 1 month or tillcure This therapy is administered to adult patients only (1ndash5)Loss of appetite Leaf decoction is given orally before each meal twice daily for 15 daysLeaf powder is given orally after each meal for 15 days (1 2 6)Palpitation of heart Leaf extract mixed with honey is given orally twice a day for 7 daysor till cure (1ndash5)Paronychia or whitlo Whole plant paste is applied externally (1ndash5)Pimples Fresh leaf extract is given orally twice daily with cow milk for 2 months (1ndash5)Premature graying of hair Fresh leaf extract is gently applied to hair (1ndash5)Skin diseases Plant paste is applied externally for 15 days in eczema Leaf paste is appliedexternally to boils and extract is given orally twice daily for 15 days (1 2 5)Spleen enlargement Leaf extract mixed with honey is given orally twice or thrice dailyfor 15 days or till cureUrinary tract infections Plant extract is given orally twice a day for 15 days The extract isalso used to wash genitalia externally till cure (1ndash5)Weakness of vision Leaf extract is given orally twice a day with cow milk for 3 months(1ndash3)Wounds Leaf extract is used to wash open wounds (1 3 5)Wrinkles Leaf extract withWithania somnifera root powder is given orally with cowmilk twice daily for 3 months (1ndash5)

Local practitioners of Mount Abu inRajasthan India [10]

Leaves and flowers used for treatment of urinary problems jaundice asthma andcoughs

Local community of Jalalpur Jattan Gujratdistrict Punjab Pakistan [11] Leaf paste applied to treat allergy atheletersquos foot and ringworm

Santal tribe residing inThakurgaon districtBangladesh [12]

Diabetes Leaves of white-flowered plant are mixed with leaves of Scoparia dulcis leavesof Cynodon dactylon and water and then boiled in an earthen vessel The water is thenstrained through cloth and given to diabetic patients to be taken orally in the morningand evening on an empty stomach

Inhabitants of Mansoora Malegaon India[13]

Plant is used as tonic deobstruent emetic and considered useful in enlargement of liverand spleen

Chakma tribe of Tripura State India [14] Two teaspoons of leaf juice is administered daily against hepatic disorders

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

6 International Scholarly Research Notices

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulations

Local people and tribal communities ofHanumangarh District Rajasthan India [15]

Plant is used as hair tonic Extracted oil is used as tonic Leaf juice is taken orally withhoney in jaundice and dysentery The plant is considered to stimulate the digestivesystem augment appetite and improve digestion Leaf extract is given orally with waterfor diarrhea The root is considered purgative and used in conditions of liver spleen anddropsy

Inhabitants of Thar Desert India [16]Whole plant is considered deobstruent antihepatotoxic anticatarrhal and febrifugeUsed in hepatitis spleen enlargements and skin diseases Leaf is used to promote hairgrowth Leaf extract in oil is applied to scalp before bedtime for insomnia

Local communities and ethnic groups ofBundelkhand Uttar Pradesh India [17] Decoction of plant used to treat scorpion sting

Local herbalists of Samba District of Jammuand Kashmir State India [18]

Whole plant is used in asthma bronchitis fever gastric and hepatic disorders jaundiceulcers wounds sores and leucoderma

Folk medicinal practitioners of RampalBagerhat District Bangladesh [19] Whole plant used to treat indigestion

Tribals of Buldhana District MaharashtraIndia [20] Whole plants and leaves used to treat wounds

Malayali tribals of Kolli Hills Eastern GhatsTamil Nadu India [21] Whole plant juice is given orally to treat snake bite

Local people of Javadhu Hills Tamil NaduIndia [22] Plant is used for treatment of hepatitis

Malayaraya tribes of Vannapuram villageIdukki Kerala India [23] Whole plant is used for rejuvenating hair kidneys and liver

Women of Kaibarta community of AssamIndia [24]

Shoot juice with few drops of mustard oil or root extracts are given once daily for 3-4days for diarrhea

Local people of Mandi Bahauddin DistrictPakistan [25] Leaf paste applied for allergy athletersquos foot and ringworm

Anyi-Ndenye pregnant women of EasternCote drsquoIvoire Africa [26] Whole plant used to ensure fetal development and facilitate childbirth

Local people of Dibrugarh Assam India [27] Whole plant used as tonic and for treatment of spleen enlargementWomen of Azamgarh District Uttar PradeshIndia [28] Whole plant juice with sugar is given to persons suffering from severe whitish dysentery

Villagers of Nizamabad District AndhraPradesh India [29]

Dry plant powder is given to elderly people to provide energy Plant paste is applied tohead to blacken gray hair

Traditional herbal medical practitioners ofNagapattinam District Tamil Nadu India[30]

Leaf extract is applied on swellings

Local people of Birbhum District in WestBengal India [31]

Fresh leaves are applied with sesame oil to cure baldness elephantiasis and headacheJuice of whole plant is applied in skin disorders on affected areas of skin

Saperas community of Khetawas JhajjarDistrict Haryana India [32] Treatment of snake bite

Local traditional healers of Western UttarPradesh India [33] Decoction of whole plant is given for scorpion sting

Bhil Pawara and Pardhi tribes in SatpudaMountain of Nandurbar Dhule and Jalgaondistrict of Maharashtra India [34]

4-5 powdered leaves are administered with a cup of water in a single dose for 2 days formenorrhagia

Uraly tribes of Idukki District Kerala India[35] Crushed leaves are applied on cuts and wounds

Local inhabitants of rural and remote areasof Kalyanpur block of Kanpur District UttarPradesh India [36]

2ndash5 g leaf paste is applied on fresh cuts and wounds

Gujjar tribes in the Shivalik Hills ofHaridwar Uttarakhand India [37] Jaundice premature graying and falling of hair

Tribes of ParambikulamWildlife SanctuaryKerala India [38] Leaf paste is applied to hair to promote growth

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

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Volume 2014

ToxinsJournal of

VaccinesJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 7

Table 3 Continued

Location and tribenature of user(s) Plant part(s) used diseases treated formulationsLocal people and traditional healers ofAmbala District Haryana India [39]

Leaf decoction is put on head to cure headache Leaf extract is given to cure asthma coldand for hair cleaning and lice

Traditional healers and local people ofArghakhanchi District Nepal [40] Plant juice is applied externally in cuts and wounds

Ethnic communities of Moradabad DistrictWestern Uttar Pradesh India [41] Leaf extract is applied to head to get rid of dandruff and to blacken gray hair

Tribals of Boudh District Odisha India [42] Whole plant is grounded with black pepper and made into small pills Two pills areadministered twice a day to infants for treatment of jaundice and fever

the combined extract At the same time changes in bio-chemical parameters like total protein total bilirubin totalcholesterol triglycerides and urea were restored to nearnormal levels with the combined extract [48]

Administration of fresh leaf powder (500mgkg) to ratswas observed to lead to significant hepatoprotective actionin paracetamol-induced liver toxicity in rats Histopatho-logical studies indicated that paracetamol-administered ratliver showed severe congestions hydropic degenerationand occasional necrosis while leaf-administered rat livershowed decreased hepatocyte damage At the same timeparacetamol-induced elevated levels of serum ALT ASTalkaline phosphatase (ALP) LDH and GGT as well asparacetamol-induced changes in serum proteins bilirubincholesterol and triglycerides were restored to normal levelswith the leaf powder [49]

In CCl4-induced hepatotoxicity in rats methanol extract

of leaves and chloroform extract of roots of E alba showedsignificant reductions of lysosomal enzymes in serum fromthe elevated levels induced by carbon tetrachloride At thesame timeCCl

4-induced elevated serumGOTGPTALP and

bilirubin levelswere also restored towards normalizationwithadministration of both extracts [50]

The hepatoprotective activity of ethanol extract of Ealba whole plants was studied in rats given ethanol for21 days Ethanol administration led to hepatic damage asmanifested by histopathological changes increase in thio-barbituric acid-reactive substances (TBARS) decrease inreduced glutathione (GSH) superoxide dismutase (SOD)and catalase (CAT) and increase in glutathione peroxidase(GPx) in liver Histopathological changes indicated that inalcohol-treated animals liver showed hepatocytic necrosisand inflammation in the centrilobular regionwith portal tria-ditis These toxic effects were reversed with coadministrationof extract with ethanol [51]

Aqueous extract of leaves of the plant has been foundto offer hepatoprotectivity against paracetamol-induced liverdamage Paracetamol-induced increases in TBARS werereduced by the aqueous extract and paracetamol-induceddecreases in GSH were also reversed by the extract Catalasewas also decreased in paracetamol-treated groups which wasalso reversed by coadministration of the extract [52]

The alcoholic and aqueous extract of E alba leaves wastested for hepatoprotective activity against paracetamol-induced liver damage in albino rats The alcoholicextract demonstrated significant hepatoprotective effects

The alcoholic extract-treated rats of group III revealedmarked hepatoprotection as there was significant (119875 lt 001)reduction in SGOT SGPT ALP total bilirubin and directbilirubin and a significant (119875 lt 001) increase in total proteinand albumin as compared to paracetamol treated group [53]

The aqueous leaf extract (85) of E alba was examinedfor hepatoprotective effects in CCl

4-induced hepatotoxicity

in male albino rats CCl4induced oxidative stress in rats

resulting in oxidative injury as manifested by increases inTBARS and hydroperoxides and augmented levels of serumAST ALT and ALP At the same time there were depletedlevels of SOD CAT GPx and glutathione-S-transferase(GST) The aqueous extract given at a dose of 250mg perkg body weight reversed these changes and brought themback to normal levels The results suggest that increases inoxidative stress play a vital role in development of hepaticinjury which can be ameliorated through administration ofaqueous extract of the leaves [54]

A polyherbal formulation (Ayush-Liv04) containing Ealba (along with Clitoria ternatea Asparagus racemosusAlpinia galanga and milk tuttam ie copper containingstone) showed hepatoprotective activity against CCl

4and

ethanol induced liver damage in rats Elevated levels of serumAST ALT ALP acid phosphatase and bilirubin were signif-icantly lowered in the polyherbal formulation-administeredrats [55]

The ethanolic extract of a polyherbal formulation con-taining leaves of Melia azadirachta seeds of Piper longumand whole plants of E alba has been evaluated for hepatopro-tective effects against CCl

4-induced hepatic damage in male

albino rats The substantially reduced levels of SOD CATGPx GST and glutathione reductase (GR) due to CCl

4were

restored to normal with the extract [56]Hepatoprotective effects of ethanolic extract of E alba

leaves and leaf callus were examined in a model of CCl4-

induced acute hepatotoxicity in albino rats Liver damagewas assessed bymeasuring serum parameters like GOT GPTALP albumin and total protein as well as histopathologicalexamination Oral administration of the extract at 250 and300mgkg respectively showed hepatoprotective effects asdemonstrated by restoring to near normal levels the serumparameters and improving hepatic lesions caused by carbontetrachloride [57]

42 Hair Growth Promoting Activity Petroleum ether andethanol extract of E alba has been tested in albino rats for

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

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MEDIATORSINFLAMMATION

of

8 International Scholarly Research Notices

promoting hair growth activity The extracts were incorpo-rated into oleaginous cream (water in oil cream base) andapplied topically on shaved denuded skin of male albinorats The extracts significantly reduced hair growth time byhalf as compared to nontreated control animals Quantitativeanalysis of hair growth after treatment with petroleum etherextract (5) exhibited greater number of hair follicles inanagenic phase (69 plusmn 4) which were higher as compared tocontrol (47 plusmn 13) [58]

The methanol extract of the plant has also been tested forits efficacy for promoting hair growth in pigmented C57BL6mice preselected for their telogen phase of hair growth Inthese species the truncal epidermis lacks melanin-producingmelanocytes and melanin production is strictly coupled toanagen phase of hair growth Telogen to anagen transitionwas assessed following topical administration of the extractA dose-dependent transition of telogen to anagen phaseof hair growth was observed following extract treatmentwith an extract dose of 32mg15 cm2 875 animals showedanagen phase of growth while with an extract dose of16mg15 cm2 50 of the animals showed the transition fromtelogen to anagen phase [59]

A polyherbal formulation containing E alba Hibiscusrosa-sinensis and Nardostachys jatamansi exhibited excellenthair growth activity in Wistar albino rats Hair growthinitiation time and time required for complete hair growthwere significantly reduced Treatment with the formulationresulted in greater number of hair follicles in the anagenicphase [60]

43 Antidiabetic Activity The beneficial effects of the plantin diabetes have been reported An Ayurvedic formulationconsisting ofWithania somnifera Tinospora cordifolia Ecliptaalba Ocimum sanctum Picrorhiza kurroa and shilajit atdoses of 100 and 200mgkg po administered once dailyfor 28 days to streptozotocin- (STZ-) induced diabetic maleCF strain rats induced a dose-related decrease in STZhyperglycemia and attenuation of STZ induced decrease inpancreatic islet superoxide dismutase (SOD) activity It hasbeen suggested that the STZ-induced hyperglycemia was theconsequence of decreased islet SOD in islets [61]

In alloxan-diabetic rats oral administration of leaf sus-pension of E alba (2 and 4 gkg body weight) for 60days resulted in significant reduction in blood glucose(from 3720 plusmn 332 to 1170 plusmn 228) glycosylated hemoglobinHbA(1)c a decrease in the activities of glucose-6 phosphataseand fructose 16-bisphosphatase and an increase in the activ-ity of liver hexokinase all of these activities being beneficialfor amelioration of hyperglycemia and other diabetes-relatedcomplications [62]

The antidiabetic effect of E alba ethanolic extract hasbeen investigated for possible beneficial effects against hyper-glycemia and diabetic nephropathy in STZ-diabetic ratsSingle dose treatment of the extract was found to signifi-cantly lower blood glucose level by 176 after 5 h of oraladministration at a dose of 250mgkg Treatment of STZ-diabetic animals for 10 weeks with the above dose levelsignificantly reduced the elevated levels of blood glucoseHbA1C urea uric acid and creatinine and significantly

increased the depressed serum insulin level The extractexerted a significant inhibitory effect on 120572-glucosidase in anoncompetitive manner with an IC

50value of around 54120583g

per mL and was found inhibitory to eye lens aldose reductasewith an IC

50value of about 45 120583g per mL Inhibition of 120572-

glucosidase and aldose reductase was postulated to be thereason behind the other observed effects [63] A bioactivity-guided isolation approach based on 120572-glucosidase inhibitionled to the isolation of four echinocystic acid glycosides ofwhich eclalbasaponin VI was found to be the most potent(IC50542 plusmn 13 microM) [64]

44 Analgesic and Anti-Inflammatory Activities Analgesicactivity of alcoholic extract of E alba has been determinedthrough tail flick hot plate and writhing methods in ratsand mice In all three methods the extract at a dose of200mgkg demonstrated significant analgesic and antinoci-ceptive effects [65]

Hydroalcoholic extract of the plant showed significantantinociceptive activity in acetic acid-induced writhing testsin rodent model at a dose of 200mgkg po The extractfurther showed analgesic effects in formalin tests with theinhibition occurring in the second phase of the response [66]

The analgesic activity of ethanol extract of E alba wholeplants as well as a total alkaloid fraction was seen in exper-iments with albino mice by using standard experimentalmodels such as the tail clip method the tail flick method andthe acetic acid induced writhing response The results fromthis study showed that both the ethanol extract and the totalalkaloids produced good analgesic activity in all the differentmodels of analgesia tested Total alkaloid fraction showedbetter analgesic activity than ethanolic extract [67]

The anti-inflammatory effect of the plant was evalu-ated using carrageenan mediators such as histamine andserotonin induced paw oedema and cotton pellet inducedgranuloma tests for their effect on acute and chronic phaseinflammation models in rats The results indicated potentanti-inflammatory activity of the plant in all themodels tested[68] Cumulatively the reports suggest that the plant canprove valuable as both a central and peripheral analgesicagent

45 Skin Diseases Leaves of E alba are used to get ridof ectoparasites in dogs in Trinidad and Tobago [69]An Ayurvedic formulation containing E alba powder hasbeen shown to provide complete remission to 226 andchecked the recurrence of the disease in 895 patients ofldquoVicharchikardquo (eczema) [70]

The antioxidant and protective effect of water extractof E alba against ultraviolet- (UV-) irradiation-induceddamage has been investigated The extract had a potenteffect in scavenging 22-diphenyl-1-picrylhydrazyl (DPPH)superoxide radicals and chelating ferrous ion exhibitingIC50

values respectively of 023mgmL 048mgmL and125mgmL The total phenol content of the extract was17645mg gallic acid equivalents The extract was also seento absorb UVA and UVB irradiation and demonstrated adose-dependent protection of HaCaT human keratinocytes

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 9

and mouse fibroblasts 3T3 cells against UVB-induced cyto-toxicity The protective effect against skin cell damage wasattributed to a synergistic effect between chlorogenic acid andother active components present in the extract [71]

46 Neuropharmacological Activities The aqueous andhydroalcoholic extracts of E alba have been evaluatedfor sedative muscle relaxant anxiolytic nootropic andantistress activities at doses of 150 and 300mgkg po Thefindings indicated nootropic activity of the aqueous extract(300mgkg po) and its hydrolyzed fraction (30mgkgpo) The aqueous extract and the hydrolyzed fraction wereobserved to provide protection against cold restraint inducedgastric ulcer formation and also normalized the white bloodcell count in the milk induced leukocytosis challenge model[72]

The aqueous extract of leaves of E alba has been exam-ined for its memory enhancing quality Doses of 100 and200mg of extract suspension in water (per kg body weight)were administered to rats to evaluate transfer latency (TL)on an elevated plus maze This method gives a measure ofacquisition and retrieval learning Spatial habitual learningtests were conducted with mice at the aforementioned twodoses In thismethodmice were placed at the center of open-field apparatus to assess spatial habitual learning observedfor 20 minutes for rearing and time spent during rearing for30minutes 24 hours and 96 hours and 144 hoursThe extractat both doses produced a significant decrease in TL in ratsand the amount of rearing in mice The results indicate anextract-induced improvement in cognitive functions whichwas attributed to the presence of luteolins in the extract [73]

Aqueous extract of E alba has been tested for its abilityto reduce aggression through foot shock-induced aggressionand water competition tests Minimization of aggression inboth tests was observed with the extract at doses of 100 and200mgkg [74]

Methanolic extract of E alba whole plant has beenshown to ameliorate oxidative stress-induced mitochondrialdysfunction in an animal (rat) model of Alzheimerrsquos disease(evaluation of short-term memory using elevated plus mazemodel) Mitochondrial function was determined throughMTT [3-(45-dimethylthiazol-2-yl)-25-diphenyltetrazoliumbromide] assay Synaptosomal fractions of scopolaminehydrobromide-treated rats exhibited a significant decreasein MTT reduction which was prevented by the extract ata dose of 200mgkg Scopolamine significantly increasedtransfer latency in rats indicative of amnesia or impairmentof memory Transfer latency of rats using the elevated plusmaze model was also dose-dependently decreased (rever-sal of scopolamine-induced increase) by the extract thusdemonstrating increase in memory [75] The extract showedhigh phenolic and flavonoid contents which might havecontributed to amelioration of oxidative stress

47 Antioxidant Activity The methanol and hydrolyzedextract of E alba has been assessed for its antioxidantpotential in both in vitro and ex vivo models The in vitroantioxidant activity was evaluated through 22-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and nitric

oxide radical inhibition activityThe ex vivo antioxidant activ-ity was determined through lipid peroxidation inhibitoryactivity on mice liver homogenate by thiobarbituric acid-reactive substances (TBARS)methodThemethanolic extractand hydrolyzed extract both showed potent antioxidantactivity in both models in proving to be powerful scavengersof DPPH free radicals and nitric oxide radicals as wellas being inhibitors of lipid peroxidation [76] Antioxidantactivity as assessed byDPPH free radical scavengingmethodshas also been described for ethanol extract of the plant [77]

Methanolic and aqueous extracts of E alba demon-strated antioxidant activity in hydrogen peroxide scavengingassays total antioxidant capacity and through reducingability assay [78] The antioxidant potential of the plantmethanolic extract has been shown through DPPH freeradical scavenging and 221015840-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays [79] The ethanolic extract ofthe plant also demonstrated antioxidant potential in DPPHand ABTS assays [80] Ethanol and ethyl acetate extractsof leaves of the plant showed antioxidant activity in theferric thiocyanate method aqueous and hexane extracts alsoshowed antioxidant effects but less than ethanol and ethylacetate extracts [81]

The possible cerebroprotective and antioxidant effectof hydroalcoholic extract of E alba has been evaluatedin global cerebral ischemia in rats The global cerebralischemia-reperfusion injury was induced by occluding bilat-eral common carotid arteries (BCCA) for 30min followedby 4 h reperfusion BCCA caused significant depletion insuperoxide dismutase (SOD) glutathione peroxidase (GPx)reduced glutathione (GSH) catalase (CAT) glutathione-S-transferase (GST) and glutathione reductase (GR) and signif-icant increase in malondialdehyde (MDA) in brain Pretreat-ment with hydroalcoholic extract significantly reversed thelevels of biochemical parameters and significantly reducedthe edema and cerebral infarct size as compared to theischemic control group [82]

48 Antimicrobial Activity Various solvent (petroleum etherbenzene chloroform acetone methanol and aqueous)extracts of E alba were found to be active against clinicalisolates from oral cancer cases These isolates includedvarious bacteria like Staphylococcus aureus Escherichia coliStaphylococcus epidermis Pseudomonas aeruginosa Klebsiellapneumoniae Proteus mirabilis and Proteus vulgaris andfunguses like Candida albicans and Aspergillus fumigatus[83]

Ethanol and ethyl acetate extracts of leaves of the planthave been found to be active against E coli K pneumoniaeShigella dysenteriae Salmonella typhi P aeruginosa Bacillussubtilis and S aureus with Minimum Inhibitory Concentra-tions (MIC) ranging from 45 to 90 120583LmL [81]

Hexane extract of aerial parts of the plant reportedlyshowed antibacterial activity against S aureus Bacillus cereusE coli S typhi K pneumoniae Streptococcus pyogenes and Paeruginosa whereas acetone ethanol methanol and aqueousextracts showed intermediate activity against S aureus Bcereus E coli S typhi K pneumoniae P aeruginosa Pmirabilis and S pyogenes [84] The aqueous extract showed

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

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MEDIATORSINFLAMMATION

of

10 International Scholarly Research Notices

good activity against S pyogenes B cereus E coli and Paeruginosa

The susceptibility of various extracts of E alba wastested against nine different test organisms using the welldiffusion method The n-butanol extract showed inhibitoryactivity against all nine species namely B cereus B subtilisC albicans Erwinia carotovora E coli K pneumoniaeP aeruginosa S typhi and S aureus Petroleum etherdichloromethane methanol and aqueous extracts showedvarying levels of inhibition against some of thesemicroorgan-isms [85]

Aqueous extract of leaves stems and flowers of E albahas been screened for inhibitory activity against multiple testorganisms The leaf extract was effective against Enterobac-ter cloacae and K pneumoniae stem extract was effectiveagainst E cloacae Enterococcus faecalis K pneumoniaeand Staphylococcus saprophyticus while flower extract waseffective against P vulgaris S aureus and S saprophyticus[86] Aqueous and ethanolic extracts of leaves also reportedlyshowed moderate inhibitory activities against S aureus Ecoli P vulgaris P aeruginosa C albicans and Aspergillusniger when tested by agar plate disc diffusion method [87]

Antimicrobial activity of petroleum ether ethyl acetateethanol and aqueous extract of E alba were screened forinhibitory activity by agar well diffusion method against Bsubtilis S aureus P mirabilis B cereus E coli Salmonellaenterica serv typhi P aeruginosa S epidermis and Calbicans Maximum numbers of the organisms tested wereinhibited by the ethyl acetate fractionwith zones of inhibitionranging from 11 plusmn 1mm to 22 plusmn 1mm with maximumactivity against B cereus The ethanol extract demonstratedmaximum inhibitory activity against E coli Petroleum etherextract inhibited only B cereus while aqueous extract wasfound to inhibit B subtilis B cereus S aureus andC albicans[88]

The antimicrobial activity of methanol acetone andaqueous extracts of leaves of three morphotypes of E albahas been examined by the disc diffusion method againstthe Gram positive bacteriamdashS aureus and B subtilismdashandGram negative bacteriamdashK pneumoniae E coli and Paeruginosa The extracts demonstrated inhibitory activityagainst all bacteria against P aeruginosa The aqueous extractwas found to be the least effectiveThe acetone extract showedmore antimicrobial activity against S aureus E coli andK pneumoniae than methanol extract The methanol extractshowed maximum activity against B subtilis [89]

An aqueous extract of leaves of E alba has been shown toinhibit the fungus Fusarium oxysporum as determined by theagar plate disc diffusion method [90] Methanolic extract ofaerial parts of the plant showed maximum inhibitory activityagainst S epidermis S aureus and Salmonella typhimuriumWedelolactone isolated from the ethyl acetate fraction ofaerial parts showed enhanced antimicrobial activity andas such can be the responsible agent behind the observedantimicrobial effects [91] Eclalbasaponin another phyto-chemical constituent of the plant has been shown to beresponsible for the inhibitory activity of the plant againstB subtilis and P aeruginosa [92] This inhibitory activity

has been attributed to disruption of bacterial cell membraneleading to loss of bacterial cell viability

49 Antimalarial Activity The antimalarial activity of leafextract of E alba has been tested against Plasmodium bergheiANKA strain in mice The methanolic leaf extract (250ndash750mgkg) produced a dose-dependent chemosuppressionor schizontocidal effect during early and established infectionand high mean survival time (mst) values particularly inthe group administered 750mgkgday of extract The plantextract also exhibited repository activity [93]

Mosquito larvicidal and ovicidal activities of crudehexane ethyl acetate benzene chloroform and methanolextracts of the leaves of E alba were tested against the earlythird-instar larvae of Anopheles stephensi (Liston) (DipteraCulicidae) Larval mortality was observed 24 hours fol-lowing extract exposure The highest larval mortality wasobserved with methanol extract (LC

50= 11256 ppm LC

90=

22068 ppm) Percent hatchability was also found to beinversely proportional to concentration of the extract Mor-tality of 100 was exerted with methanol extract at 200 ppmThus this plant could prove to be useful in combatingmalariathrough its larvicidal and ovicidal activities [94]

Larvicidal and ovicidal activities of benzene hexaneethyl acetate methanol and chloroform leaf extract of E albaagainst dengue vectorAedes aegypti has also been examinedMaximum larvicidal activity was observed with themethanolextract The LC

50values of benzene hexane ethyl acetate

methanol and chloroform extract of E alba against earlythird- instar larvae of A aegypti were 15138 16510 1548812764 and 14628 ppm respectively The methanol extractwas found to be most effective for ovicidal activity against Aaegypti The methanol extract exerted 100 mortality (zerohatchability) at 300 ppm [95]

The adulticidal and repellent activities of crude hexaneethyl acetate benzene chloroform and methanol extractsof leaf of E alba were assayed for their toxicity against twoimportant vectormosquitoes namelyCulex quinquefasciatusand Aedes aegypti (Diptera Culicidae) C quinquefasciatusis the vector of Wuchereria bancrofti avian malaria andarboviruses including St Louis encephalitis virus Westernequine encephalitis virus and West Nile virus All extractsshowed moderate adulticide effects The extracts also hadconcentration-dependent mosquito repellent activities [96]The methanol extract of leaves of E alba also reportedlydemonstratedmaximum adulticidal as well as repellent activ-ities against A stephensi compared to benzene hexane ethylacetate and chloroform extracts [97]

410 Cardiovascular Effects The effect of administration ofdried E alba leaf powder (3 g per day) has been studied inmild hypertensive subjects Subjects were given six capsules(500mg powder per capsule) in three doses per day for 60days When compared with placebo given control groupsthe results showed that Eclipta-supplemented group showeda marked reduction in mean arterial pressure by 15 totalcholesterol (17) low-density lipoprotein fraction (24)triglycerides (14) very-low-density lipoprotein fraction(14) and plasma lipid peroxides (18)There was a marked

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 11

increase in urine volume (34) urine sodium (24) serumvitamin C (17) and serum tocopherols (23) in the Eclipta-administered group The findings indicated that leaf powderpossessed diuretic hypotensive and hypocholesterolemicproperties and helps in the alleviation of oxidative stress-induced complications in hypertensives [98]

Ethanolic extract of leaves and leaf calluses of E albawas examined for cardiac inhibitory activity in isolated froghearts The extracts showed negative ionotropic and negativechronotropic effects as well as reduction in cardiac outputCallus extract demonstrated a higher cardiac inhibitory effectthan leaf extract at 20mg doses The callus extract was alsofound to antagonize the effects of adrenaline [57]

411 Immunomodulatory Effects The immunostimulatoryeffects of feeding aqueous extract of leaves of E albahave been studied in tilapia fish (Oreochromis mossam-bicus) Fish were fed diet containing extract at 0 00101 and 1 levels of diet After each week nonspecifichumoral (lysozyme antiprotease and complement) andcellular (myeloperoxidase content production of reactiveoxygen and nitrogen species) responses and disease resis-tance against Aeromonas hydrophila were determined Ahydrophila are Gram-negative straight rods with roundedends (bacilli to coccobacilli shape) and are regarded as bothfish and human pathogens Lysozyme activity significantlyincreased after feeding fish with aqueous extract for 1 2 or3 weeks Reactive oxygen species production and myeloper-oxidase content showed significant enhancement after 1 weekof feeding with aqueous extractThe percent mortality in fishfollowing feeding the extract also diminished significantlywhen challenged with the pathogen [99]

The immunomodulatory responses of methanol extractof whole plant of E alba (containing 16 wedelolactone)have been assessed at five dose levels (dose-response rela-tionship) ranging from 100 to 500mgkg body wt usingcarbon clearance antibody titer and cyclophosphamideimmunosuppression parameters E alba extract significantlyincreased the phagocytic index and antibody titer The 119865ratios of the phagocytic index and white blood cell (WBC)count were also significant [100]

412 Antiepilepsy Activity Methanol extraction of leaf pow-der of E alba was evaluated for its antiepileptic activitythrough Maximal Electroshock Test (MES) in rats Theextract was administered orally to rats for 7 days at dosesof 50 100 and 200mg per kg body weight One hourafter the last treatment seizures were induced in rats bydelivering electroshock of 150mA for 02 s with an elec-troconvulsiometer through a pair of ear clip electrodes Adecrease in duration of hind leg extension was taken as aparameter for anticonvulsant activity Compared to controlsrats administered extract at different doses exhibited signifi-cant decrease in the duration of time spent in extensor phasein a dose-dependent manner The antiepileptic activity wasattributed to wedelolactone luteolin and 120573-amyrin presentin the extract [101]

The anticonvulsant activity of methanol extract of E albaleaves was studied using pentylenetetrazole- and picrotoxin-induced seizure models in mice and guinea pigs Themechanism was further elucidated by studying the extractrsquosGABAA receptor modulatory activity and its effect on levelsof GABA (120574-amino butyric acid) in mice brain Potentanticonvulsant activity was demonstrated by the extract whenadministered at doses of 10ndash200mgkg with a saturationlevel at 50mgkg The observed anticonvulsant effect wasattributed to positivemodulatory effects onGABAA receptors[102] Wedelolactone and luteolin present in the extractwere hypothesized for giving the observed effect NotablyGABAA receptor dysfunction contributes to epileptogenesis[103] Wedelolactone has been reported to have selectivityand affinity towards BZD (benzodiazepine) binding site onGABAA receptors [104] Also luteolin has neuroprotectiveactivity and has affinity towards BZD binding site on theGABAA receptors [105]

E alba ethanolic leaf extracts at doses of 50 100 200and 400mgkg po were studied for anticonvulsant andmuscle relaxant activity on maximal electroshock-inducedseizures (MES) rotarod and traction test respectively inrats At doses of 200 and 400mgkg the extract reducedseizures induced by MES decreased the duration of tonichind limb extension (THLE) (by 762 and 898 resp) anddecreased motor coordination showing anticonvulsant andmuscle relaxant activity [106]

E alba ethanolic leaf extract has been shown to causethiopental sodium-induced sleeping time in rats at an earlystage and to prolong the duration of sleep at doses of 200and 400mgkg The extract at 400mgkg also decreasedlocomotor activity in rats thus showing a sedative effectUrsolic and oleanolic acids present in the extract can actas GABAA agonists and this property can be responsible forthe central nervous system (CNS) depressant effect [107]Notably CNS depressant and antiepileptic activities havebeen reported for methanolic extract of leaves of Ipomoeaaquatica [108]

413 Snake Bite Extract of E alba has been shown to inhibitsnake venom phospholipase A2 activity of Crotalus durissusterrificus venom The inhibitory activity has been attributedto the coumestans wedelolactone and demethylwedelolac-tone present in the extract [109]

414 Anticancer Activity Theanticancer potential of hydroal-coholic extract of E alba has been evaluated The extractinhibited the cell proliferation in dose-dependent mannerin HepG2 A498 and C6 glioma cell lines with an IC

50of

22 plusmn 29 25 plusmn 36 and 50 plusmn 87 120583gmL respectively Theexpression of matrix metalloproteinases (MMP) 2 and 9was downregulated significantly Additionally downregula-tion of nuclear factor 120581B (NF120581B) was also observed DNAdamage was observed following 72 h of extract treatmentleading to apoptosis [110] Hydroalcoholic extract of the plantalso demonstrated antiproliferative activities in multidrug-resistantDR-HepG2 cells a hepatocellular carcinoma cell line[111]

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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MEDIATORSINFLAMMATION

of

12 International Scholarly Research Notices

Juice obtained from E alba was shown to inhibit themigration of HCC-S102 (hepatocellular carcinoma) cells Invarious human cancer cell lines of different tissue origins(liver lung and breast) the juice inhibitedmigration of all thecell lines with IC

50values ranging from 31ndash70120583gmL Thus

the plant has potential for preventing cancer metastasis [112]Antiangiogenic activity was also demonstrated with the juice

The ethyl acetate methanol and aqueous extracts ofwhole dried plants ofE albawere assessed for their inhibitoryeffects on the human lung epithelial adenocarcinoma cell line(HCC-827) using the MTT assay Dose-dependent reduc-tions in viable cell count were noticed with all three extractswith the ethyl acetate extract showing the most potency Allextracts induced apoptosis in the cancer cells [113]

Ethinylestradiol is widely used in various contraceptivesand for treatment of metabolic and sexual disorders It is alsoa genotoxic and a tumor initiating agent The treatment of10 120583M of ethinylestradiol along with 102 times 10minus4 2125 times 10minus4315 times 10minus4 and 417 times 10minus4 gmL acetone extract of E albaleaves resulted in a significant dose-dependent decrease inthe genotoxic effects induced by the treatment of 10 120583M ofethinylestradiol in cultured human lymphocytes [114]

Crude methanol extract of E alba has been shown toinhibit growth of colon cancer cells [115] The methanolicextract of the aerial parts of the plant showed inhibitoryactivity on the proliferation of hepatic stellate cells orHSCs Activity-guided fractionation led to the isolation offive oleanane-type triterpenoids echinocystic acid eclalbas-aponin II eclalbasaponin V eclalbasaponin I and eclalbas-aponin III which are all echinocystic acid derivatives Amongthe five echinocystic acid derivatives isolated echinocysticacid and eclalbasaponin II significantly inhibited the prolif-eration of HSCs in dose- and time-dependent manners [116]

415 Antiulcer Activity The ethanolic extract of E alba hasbeen examined for its antiulcer effects in several ulcer modelsin rats like cold resistant stress (CRS) and pylorus ligation(PL) The extract administered orally twice daily at dosesof 50 100 and 200mgkg was found to dose-dependentlyand significantly reduce ulcerative lesions At the same timeextract administration led to significant attenuation of lipidperoxidation and elevated levels of catalase activity Antise-cretory activity of the extract was evidenced by significantreduction in gastric volume acid output and increase ingastric pH when compared to control (without extract) rats[117]

The methanolic extract of E alba also showed antiulceractivity in ulcers induced in thirty- six-hour fasted SpragueDawley rats by aspirin or ethanol or pylorus ligation plusaspirin treatment In all the three separate experimentsthe group receiving oral administration of E alba prior toulcer induction showed highly significant reduction in theoccurrence of gastric ulcers as well as gastric inflammation(after 4 h of treatment) as compared to the control groupsThe extract activity was comparable to the activity of theproton pump inhibiting drug rabeprazole [118]

416 Anthelmintic Activity The methanol extract of wholeplant of E alba was evaluated for its anthelmintic potentialagainst the earthworm Pheretima posthuma at doses of 25ndash100mgmLThe extract exhibited paralysis of worms at dosesof 50 75 and 100mgmL and caused death of worms at 75and 100mgmL [119] The ethanol and aqueous extract alsoshowed anthelmintic activity against P posthuma [120]

5 Pharmacological Activity Reports onE alba Phytoconstituents

51 Wedelolactone In vitro 5-lipoxygenase inhibition bywedelolactone has been reported [121] 5-Lipoxygenase (5-LO) catalyzes the two-step conversion of arachidonic acid toleukotriene A4 (LTA4) [122]

A study with synthetically prepared wedelolactone andderivatives showed that both the parent compound andmost of the wedelolactone derivatives significantly protectedprimary cultured liver cells from the toxicity of CCl

4 galac-

tosamine (Galc) and phalloidin and strongly inhibited theactivity of 5-lipoxygenase in porcine leukocytes The syn-thetic wedelolactonewas also found to have stimulatory effecton the RNA synthesis in isolated nuclei from hepatocytes[123]

Ethanolic extract of the aerial parts of E alba has beenshown to neutralize the lethal activity of the venom of SouthAmerican rattlesnake (Crotalus durissus terrificus) whenmixed in vitro before ip injection into adult Swiss miceThree phytoconstituents isolated from the plant namelywedelolactone (054mganimal) sitosterol (23mganimal)and stigmasterol (23mganimal) were able to neutralizethree lethal doses of the venom Aqueous extracts of theplant inhibited the release of creatine kinase from isolated ratmuscle exposed to the crude venomThis protection was alsoobserved in vivo when the venomwas preincubated with theextract prior to injection into mice [124]

The antimyotoxic and antihemorrhagic effects of Ealba and three of its constituents wedelolactone sitosteroland stigmasterol have been investigated for their abilityto protect against myotoxicity of crotalid venoms (Both-rops jararaca Bothrops jararacussu and Lachesis muta) andpurified myotoxins (bothropstoxin BthTX bothropasin andcrotoxin) through quantification in vitro by the releaserate of creatine kinase (CK) from rat or mouse extensordigitorum muscles and in vivo by the plasma CK activityin mice Wedelolactone was more effective than sitosterol orstigmasterol to neutralize in vitromyotoxicity of the crotalidvenoms and myotoxins The in vivo myotoxicity of venomsand myotoxins was also neutralized by preincubation withwedelolactone Intravenous administration of wedelolactoneattenuated the increase in plasma CK activity induced bysubsequent intramuscular injections of the crotalid venomsor the myotoxins Wedelolactone inhibited the hemorrhagiceffect of B jararaca venom as well as the phospholipase A2activity of crotoxin and the proteolytic activity of B jararacavenom These effects have been attributed to antiproteolyticand antiphospholipase A2 activities of the constituents [125]Wedelolactone also antagonized the myotoxic activity inmice of venoms from Crotalus viridis viridis and Agkistrodon

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 13

contortrix laticinctus and two phospholipase A2 myotoxinsCVVmyotoxin andACLmyotoxin isolated from them [126]

Wedelolactone has been found to inhibit lipopolysaccha-ride- (LPS-) induced caspase-11 (an inflammatory caspase)expression in cultured cells by inhibiting NF-120581B-mediatedtranscription It has further been shown that wedelolactoneis an inhibitor of IKK (I120581B part of the upstream NF120581Bsignal transduction cascade) a kinase critical for activationof NF-120581B by mediating phosphorylation and degradationof I120581B120572 [127] Wedelolactone also reportedly significantlyinhibited the protein expression levels of iNOS (induciblenitric oxide synthase produced after activation by endotox-ins or cytokines and generating copious amounts of NO)and COX-2 (cyclooxygenase-2 converts arachidonic acid toprostaglandins resulting in pain and inflammation) in LPS-stimulated RAW 2647 cells as well as the downstream prod-ucts including NO (nitric oxide) PGE2 (prostaglandin E2)and TNF-120572 (tumor necrosis factor-120572) Moreover wedelolac-tone also inhibited LPS-inducedNF-120581B p65 activation via thedegradation and phosphorylation of I120581B-120572 and subsequenttranslocation of the NF-120581B p65 subunit to the nucleus [128]This suggests that the compound can be used as an anti-inflammatory agent

Bioassay-guided fractionation for anti-HIV-1 (humanimmunodeficiency virus 1) integrase activity led to isola-tion of six compounds from E alba extractThey were identi-fied as 5-hydroxymethyl-(22101584051015840210158401015840)-terthienyl tiglate 5-hy-droxymethyl-(22101584051015840210158401015840)-terthienyl agelate 5-hydroxymeth-yl-(22101584051015840210158401015840)-terthienyl acetate ecliptal orobol and wede-lolactoneWedelolactone showedmaximum anti-HIV-1 inte-grase inhibitory activity with an IC

50value of 40 plusmn 02

microns This study supports the use of E alba in acquiredimmunodeficiency syndrome (AIDS) patients [129]

Wedelolactone isolated fromWedelia chinensis has beenfound to modulate the androgen receptor (AR) activationof transcription from prostate-specific antigen promoter inprostate cancer (PCa) cells [130] The anticancer activity ofwedelolactone has also been shown in androgen receptor-negative MDA-MB-231 breast cancer cells where wedelolac-tone suppressed growth and induced apoptosis Cells werearrested at the S and G2M phase of the cell cycle withinduction of DNA damage Wedelolactone was found tointeract with dsDNA and inhibited the activity of DNAtopoisomerase II120572 [131]

In Chlamydia trachomatis-infected HEp-2 cells (humanepithelial type 2 cells considered to originate from ahuman laryngeal carcinoma) wedelolactone was found toinduce apoptosis in combination with LPS and polyIC(polyinosinicpolycytidylic acid) leading to lesser viability ofChlamydia [132]

G protein-coupled receptor-35 (GPR35) has been shownto be a target of the asthma drugs cromolyn disodium andnedocromil sodium Wedelolactone which is antiallergicwas found to be a potent120573-arrestin-biasedGPR35 agonist andcan be considered a potential drug against asthma [133]

Adipocyte hyperplasia is associated with obesity andarises due to adipogenic differentiation of resident multi-potent stem cells in the vascular stroma of adipose tissueand remote stem cells of other organs [134] Wedelolactone

has been observed to inhibit the adipogenic differentiationof human adipose tissue-derived mesenchymal stem cells(hAMSCs) It has been shown that this process may bemediated through the ERK (extracellular signal regulatedkinase) pathway [135]

Metabolism of arachidonic acid through the 5-lipoxygen-ase pathway has been shown to play a critical role in the sur-vival of prostate cancer cells Wedelolactone has been foundto kill both androgen-sensitive and androgen-independentprostate cancer cells in a dose-dependentmanner by inducingapoptosis Wedelolactone-induced apoptosis was dependenton c-JunN-terminal kinase (c-JNK) and caspase-3 Apoptosiswas triggered via downregulation of protein kinase C120576 butwithout inhibition of Akt (protein kinase B) suggesting thata novel mechanism is at work [136] Notably JNK plays acritical role in death receptor-initiated extrinsic as well asmitochondrial intrinsic apoptotic pathways through mod-ulating the activities of mitochondrial pro- and antiapop-totic proteins through distinct phosphorylation events [137]Caspase-3 is a death protease and is frequently involved inapoptosis [138] Downregulation of protein kinase C120576 hasalso been shown to occur using tumor necrosis factor-relatedapoptosis inducing ligand (TRAIL) stimulated glioma cellshowever in this case reduced expression of Akt was alsoobserved [139]

Wedelolactone has been reported to synergize withinterferon-120574 (IFN-120574) to induce apoptosis in tumor cells Thecompound increased IFN-120574 signaling by inhibiting STAT1(signal transducer and activator of transcription 1 protein)dephosphorylation and prolonging STAT1 activation throughspecific inhibition of T-cell protein tyrosine phosphatase(TCPTP) an important tyrosine phosphatase for STAT1dephosphorylation [140] STAT1 has been implicated inmodulating pro- and antiapoptotic genes following stress-induced responses [141]

Wedelolactone has been reported to exhibit antifibroticeffects on human hepatic stellate cell line LX-2 The com-pound reduced the cellular viability of LX-2 in a time- anddose-dependent manner Wedelolactone induced apoptosisof LX-2 cells by decreasing the expression of antiapoptoticBcl-2 and increasing the expression of proapoptotic Bax Theinhibition of activation of LX-2 cells has been demonstratedand attributed by the authors to a number of reasons includ-ing inducing Bcl-2 family involved apoptosis upregulatingphosphorylated status of ERK and JNK expressions andinhibiting nuclear factor-120581B (NF-120581B) mediated activity [142]

Overall the various reports indicate that the compoundhas antiinflammatory hepatoprotective snake venom neu-tralizing anti-HIV anticancer and antiasthmatic effects

52 Eclalbasaponins The antiproliferative effect of eclalbas-aponinsisolated from E alba on hepatic stellate cells haspreviously been described [116] Eclalbasaponin I isolatedfrom aerial parts of the plant reportedly dose-dependentlyinhibited the proliferation of hepatoma cell smmc-7721with IC

50value of 1111703 120583gmL [143] Eclalbasaponin VI

isolated from E alba has been shown to demonstrate120572-glucosidase activity [64] Eclalbasaponin isolated from

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

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AddictionJournal of

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Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

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Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

14 International Scholarly Research Notices

E alba has been shown to demonstrate antibacterial activity[92]

Echinocystic acid isolated from ethyl acetate fraction of70 ethanol extract of the plant inhibited LPS-induced pro-duction of nitric oxide and cytokines such as tumor necrosisfactor-120572 and interleukin-6 in RAW 2647 macrophages Thecompound also inhibited LPS-induced inducible nitric oxidesynthase expression at the protein level and inducible nitricoxide synthase (iNOS) tumor necrosis factor-120572 (TNF-120572) andinterleukin-6 (IL-6) expression at the mRNA level and inhib-ited LPS-induced iNOS promoter binding activity Addi-tionally echinocystic acid suppressed the lipopolysaccharide-induced transcriptional activity of nuclear factor-120581B byblocking the nuclear translocation of p65 [144] Thus thiscompound can be regarded as a potent anti-inflammatoryagent

Taken together eclalbasaponins possess anticancer andanti-inflammatory effects

53 120572-Amyrin Reports on 120572-amyrin are few however sev-eral reports are present on pharmacological effects of acombination of 120572- and 120573-amyrin (ABA) as well as 120572-amyrinderivatives Antilipoxygenase activity has been reported for120572-amyrin acetate suggesting its possibly beneficial role inarthritis [145] In adult male Wistar rats made arthritic bysubplantar injection of complete Freundrsquos adjuvant 120572-amyrinpalmitate caused increases in serum hyaluronate and bloodgranulocytes toward nonarthritic levels and corrected themoderate anemia of adjuvant arthritis [146] The triterpenes120572-amyrin and its palmitate and linoleate esters caused growthinhibition of rat osteosarcoma cells and tadpole collagenasedigestion of type I (bone) native collagen The antiarthriticeffect has been attributed to inhibition by the triterpenes ofjoint destruction [147]

ABA isolated from the resin of Protium kleinii causeddose-dependent and significant antinociception against thevisceral pain in mice produced by (intraperitoneal) ipinjection of acetic acid ip po intracerebroventricular(icv) or intrathecal (it) administration of ABA inhibitedboth neurogenic and inflammatory phases of the overt noci-ception caused by intraplantar (ipl) injection of formalinABA given by ip po it or icv routes inhibits theneurogenic nociception induced by capsaicin In additionip treatment with ABA was able to reduce the nociceptionproduced by 8-bromo-cAMP (8-Br-cAMP) and by 12-O-tetradecanoylphorbol-13-acetate (TPA) or the hyperalgesiacaused by glutamate [148]

Anti-inflammatory effect of 120572-amyrin isolated from Pkleinii has been demonstrated through its ability to inhibitboth ear edema and influx of polymorphonuclear cells inresponse to topical application of 12-O-tetradecanoylphor-bol-acetate (TPA) in mice ears [149] In TPA-induced skininflammation in mice topical application of 120572-amyrin inhib-ited TPA-induced increase of prostaglandin E2 (PGE2) levels120572-Amyrin also prevented I120581B120572 degradation p65RelA phos-phorylation and NF-120581B activation In addition 120572-amyrinalso inhibited the activation of upstream protein kinasesnamely ERK p38mitogen-activated protein kinase (MAPK)

and protein kinase C (PKC) 120572 The anti-inflammatorymechanism has been proposed to be suppression of COX-2expression through inhibition of ERK p38MAPK andPKC120572as well as blocking NF-120581B activation [150]

ABA isolated from Protium heptaphyllum significantlyattenuated cerulein-induced acute pancreatitis in miceDecreases in cerulein-induced increases of tumor necrosisfactor TNF-120572 interleukin-6 lipase amylase myeloperoxi-dase (MPO) and TBARS were noted with administration ofABA Moreover ABA significantly suppressed the pancreaticedema inflammatory cell infiltration acinar cell necrosisand expressions of TNF120572 and iNOS [151] Similar protectiveeffect of ABA was also seen in acute pancreatitis induced inrats with L-arginine [152]

ABA (3ndash100mgkg) isolated from Protium heptaphyl-lum resin demonstrated significant antinociceptive activityagainst either subplantar (16 120583g) or intracolonic applicationof capsaicin inmice [153] antinociceptive activity of ABA hasalso been reported in mice for cyclophosphamide-inducedbladder pain and intracolonic administration of mustard oil[154]

The protective effect of ABA has been demonstratedagainst trinitrobenzene sulphonic acid- (TNBS-) inducedcolitis in Swiss male mice [155] The results indicated thatABA suppresses inflammatory cytokines and COX-2 levelspossibly via inhibition of NF-120581B and CREB-signaling path-ways The preventive effect of ABA against dextran sulfate-induced colitis in mice has also been demonstrated it hasbeen hypothesized that the cannabinoid pathway may beinvolved [156]120572-Amyrin acetate isolated from Tylophora hirsuta tested

positive for antispasmodic activity on spontaneous rabbitsrsquojejunum preparations with EC

50value of (60 plusmn 2) times 10(minus5)M

The compound also tested positive on KCl induced contrac-tions with EC

50value of (72 plusmn 3) times 10(minus5)M The compound

thus can prove to be of use against gastrointestinal disorderslike diarrhea and dysentery [157]

ABA isolated from the resin of Protium heptaphyllummanifested a hypolipidemic effect in normoglycemic miceand reduced the elevated plasma glucose levels during oralglucose tolerance tests STZ-induced diabetic mice showedsignificant decreases in blood glucose (BG) total cholesterol(TC) and serum triglycerides (TGs) when treated withABA Histopathological studies showed the beneficial effectof ABA on pancreas in maintaining 120573-cell integrity In highfat diet- (HFD-) fed mice oral administration of ABA (1030 and 100mgkg) the HFD-associated rise in serum TCand TGs was significantly less particularly at a dose of100mgkg At this dose there were significant decreasesin very low-density lipoprotein (VLDL) and low- densitylipoprotein (LDL) cholesterol and an elevation of high densitylipoprotein (HDL) cholesterol The atherogenic index wasalso significantly reduced by ABA [158]120572-Amyrin acetate isolated from aerial roots of Ficus

benghalensis has been shown to reduce hyperglycemia andimprove diabetic conditions in STZ-induced diabetic rats anddbdb diabetic mice [159]

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 15

120572-Amyrin isolated from Rhaponticum carthamoides hasbeen shown to induce proliferation of human keratinocytes(HaCaT) by about 18 [160]120572-Amyrin acetate at concentrations of 16 caused 769

mortality rate in adult femaleA stephensimosquitoes In vivoexposure of the mosquitoes to the compound was found toincreasemean probing time and decrease blood engorgementtime and feeding rate and a declination in fecundity whichreduced the overall survival and reproductive capacity of themalaria vector A stephensi [161]

ABA from the stem bark resin of Protium heptaphyllumshowed anxiolytic and antidepressant effects when testedin mice by the open-field elevated plus maze rotarodforced swimming and pentobarbital-induced sleeping timeIt has been hypothesized that the anxiolytic effect mayinvolve benzodiazepine-type receptors while the antidepres-sant effect may involve noradrenergic mechanisms [162]

Hepatoprotective action of ABA has been reportedagainst acetaminophen-induced liver injury in mice ABAwas isolated from the trunk wood resin of Protium hepta-phyllum Acetaminophen (500mgkg po) caused fulminantliver damage characterized by centrilobular necrosis withinflammatory cell infiltration an increase in serum ALT andAST activities a decrease in hepatic glutathione (GSH) and50 mortality Pretreatment with ABA (50 and 100mgkgip at 48 24 and 2 h before acetaminophen) attenuatedthe acetaminophen-induced acute increase in serum ALTand AST activities increased the depleted hepatic GSHand considerably reduced the histopathological alterationsFurthermore ABA potentiated the pentobarbital (50mgkgip) sleeping time The results suggest that the hepatopro-tective action of ABA involved possible suppression of livercytochrome P450 and diminution in oxidative stress andtoxic metabolite formation in liver [163]

ABA isolated from Protium heptaphyllum resin showedgastroprotective effect against ethanol-induced gastricmucosal damage in mice Maximal gastroprotection wasobserved with a 100mgkg dose of ABA which was almostabolished in mice with their sensory afferents chemicallyablated by a neurotoxic dose of capsaicin It has beensuggested that the gastroprotective mechanism of ABAinvolves at least in part the activation of capsaicin-sensitiveprimary afferent neurons [164]

ABA isolated from Protium heptaphyllum resin report-edly significantly inhibited the scratching behavior inducedby dextran T40 and compound 4880 in miceThe inhibitionhas been attributed to a stabilizing action on mast cellmembrane [165]

The available scientific literature suggests that 120572-amyrinand derivatives by themselves or a combination of 120572 and120573-amyrins have diverse pharmacological activities includingantiarthritic analgesic anti-inflammatory antispasmodicantidiabetic cholesterolemic antimalarial anxiolytic antide-pressant hepatoprotective and gastroprotective activitiesand also may be beneficial against pancreatitis and pruritus

54 Miscellaneous Phytochemical Constituents of E albaSeveral phytochemical constituents of E alba have reportedmultiple and diverse pharmacological activities which will

only be briefly discussed Oleanolic acid is known for bothantidiabetic and anticancer effects It can directly modulateenzymes connected with insulin biosynthesis secretion andsignaling [166] Many of its effects are mediated throughactivation of the transcription factor Nrf2 (nuclear fac-tor erythroid 2-related factor 2) Nrf2 can modulate theexpression of more than 200 genes that are crucial in themetabolism of drugs and toxins protection against oxidativestress and inflammation and maintaining protein stabilityand degradation Nrf2 can interact with tumor suppressorprotein 53 (p53) and so control cell cycle andNF-120581BThroughthese interactions Nrf2 plays a major role in protectingagainst many age-related diseases including cancer and neu-rodegeneration as well as increasing longevity [167]

In tumor cells a recent review has pointed out that thecompound can modulate multiple signaling pathways likeNF-120581b AKT signal transducer and activator of transcription3 mammalian target of rapamycin caspases intercellularadhesion molecule 1 vascular endothelial growth factor andpoly (ADP-ribose) polymerase [168] As such oleanolic acidcan be a potential preventive as well as a therapeutic agent forcancer

Ursolic acid has been shown in various reports to haveantioxidative anticancer and anti-inflammatory propertiesalthough a recent review has pointed out that proinflamma-tory properties of the compound have also been reportedin normal cells and tissues [169] A number of reports haveshown ursolic acid to have anticancer cytotoxic antitumorantioxidant anti-inflammatory antiwrinkle anti-HIV acetylcholinesterase 120572-glucosidase antimicrobial and hepatopro-tective activities (reviewed in [170])

Oleanolic and ursolic acids have reportedly hepatoprotec-tive anti-inflammatory and antihyperlipidemic properties[171] Oleanolic and ursolic acids can also be potentiallyuseful in neurodegenerative disorders like Alzheimerrsquos dis-ease [172] A review study has described the anticancereffects of ursolic acid to include protection of cellularDNA from damage inhibition of epidermal growth factorreceptormitogen-activated protein kinase signal or of FoxM1transcription factors antiangiogenesis (which can inhibittumor cell growth) inhibition of tumor cell migration andinvasion and inducing apoptosis in cancer cells [173] Theforkhead transcription factor or FoxM1 has been shownto bind and regulate a group of genes which are mainlyinvolved in controlling late cell cycle events in the G2 and Mphases [174] Inhibition of FoxM1 expression has been foundto diminish the proliferation and anchorage-independentgrowth of breast cancer cells [175]

Antioxidant anti-inflammatory and antiallergic activi-ties have been described for luteolin The compound mayalso have cardioprotective effect [176] Luteolin has alsobeen described to have the ability to block the developmentof cancer cells both in vitro and in vivo through offer-ing protection from carcinogenic stimuli inhibiting tumorcell proliferation and induction of cell cycle arrest andorapoptosis [177] Furthermore luteolin can sensitize cancercells to therapeutic-induced cytotoxicity through a varietyof mechanisms including suppression of cell cycle pathways

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

16 International Scholarly Research Notices

like phosphatidylinositol 31015840-kinase (PI3K)Akt NF-120581B andX-linked inhibitor of apoptosis protein (XIAP) and stimu-lating apoptosis pathways including those that induce thetumor suppressor p53 [178] Modulation of reactive oxygenspecies (ROS) levels inhibition of topoisomerases I and IIreduction of NF-120581B and AP-1 activity stabilization of p53and inhibition of PI3K STAT3 insulin-like growth factor1 receptor (IGF1R) and human epidermal growth factorreceptor 2 (HER2) have also been described as the causesbehind the cancer chemopreventive and chemotherapeuticpotential of luteolin [179] It is to be noted that overexpressionof HER2 is associated with certain aggressive forms of breastcancer

The cardioprotective role of luteolin has been shown incardiomyocytes following ischemia-reperfusion suggestingthat the compound can form the basis for preventing andtreating cardiovascular diseases [180]

Apigenin has been described as a chemopreventiveagent [181] The compound also has antioxidant and anti-inflammatory properties The compound may also have abeneficial effect in cardiovascular and neurological disorders[182] A recent review has pointed out that apigenin caninhibit cancer cell growth sensitize cancer cells to elimi-nation by apoptosis and hinder the development of bloodvessels to serve the growing tumor Apigenin is able toreduce cancer cell glucose uptake inhibit remodeling ofthe extracellular matrix inhibit cell adhesion molecules thatparticipate in cancer progression (like VCAM-1 [183]) andoppose chemokine signaling pathways that direct the courseof metastasis into other locations For instance apigenin hasbeen shown to suppress migration and invasion of trans-formed cells through downregulation of C-X-C chemokinereceptor 4 expression [184] All of these effects have thenet result of blocking progression and metastasis of cancer[185] In head and neck cancers apigenin may act throughinhibiting GLUT-1 expression [186]

6 Conclusion

The plant E alba is regarded by traditional medicinalpractitioners as a valuable medicinal plant particularly forthe treatment of liver disorders gastrointestinal disordersrespiratory tract disorders hair loss skin disorders and feverScientific evidences have validated most of the claims of theethnomedicinal uses including that of treatment of snakebite with the plant Various important phytochemicals havebeen isolated and identified from the plantThese compoundsinclude wedelolactone eclalbasaponins 120572-amyrin ursolicacid oleanolic acid luteolin and apigenin The availablescientific reports indicate that these compounds can formthe next generation of drugs to treat cancer arthritis liverdiseases hair loss and snake bites

Conflict of Interests

The authors declare that they have no competing interests

Authorsrsquo Contribution

Rownak Jahan Abdullah Al-Nahain Snehali Majumder andMohammed Rahmatullah gathered and analyzed the avail-able scientific reports on the plant along with ethnomedicinalreports Mohammed Rahmatullah and Rownak Jahan ana-lyzed the data and wrote the paper All authors edited thepaper and read and approved the final paper

References

[1] C P Khare Indian Medicinal Plants An Illustrated DictionarySpringer Berlin Germany 2007

[2] N M Mithun S Shashidhara and R Vivek Kumar ldquoEcliptaalba (L) A review on its phytochemical and pharmacologicalprofilerdquo Pharmacologyonline vol 1 pp 345ndash357 2011

[3] K Ma-Ma N Nyunt and K M Tin ldquoThe protective effectof Eclipta alba on carbon tetrachloride-induced acute liverdamagerdquo Toxicology and Applied Pharmacology vol 45 no 3pp 723ndash728 1978

[4] H Wagner B Geyer Y Kiso H Hikino and G S RaoldquoCoumestans as the main active principles of the liver drugsEclipta alba and Wedelia calendulaceardquo Planta Medica vol 5pp 370ndash374 1986

[5] V N Murthy B P Reddy V Venkateshwarlu and C K KokateldquoAntihepatotoxic activity ofEclipta alba Tephrosia purpurea andBoerhaavia diffusardquo Ancient Science of Life vol 11 pp 182ndash1861992

[6] R K Upadhyay M B Pandey R N Jha and V B PandeyldquoEclalbatin a triterpene saponin from Eclipta albardquo Journal ofAsian Natural Products Research vol 3 no 3 pp 213ndash217 2001

[7] M Zhang Y Y Chen X H Di and M Liu ldquoIsolation andidentification of ecliptasaponin D from Eclipta alba (L) hasskrdquoYao Xue Xue Bao vol 32 no 8 pp 633ndash634 1997

[8] M Zhang and Y Chen ldquoChemical constituents of Eclipta alba(L) Hasskrdquo Zhongguo Zhong Yao Za Zhi vol 21 no 8 pp 480ndash510 1996

[9] A V Khan and A A Khan ldquoEthnomedicinal uses of Ecliptaprostrta Linnrdquo Indian Journal of Traditional Knowledge vol 7no 2 pp 316ndash320 2008

[10] A Gautam and A Batra ldquoEthnomedicinal plant product usedby the local traditional practitioners in Mount Aburdquo WorldJournal of Pharmaceutical Sciences vol 1 no 1 pp 10ndash18 2012

[11] K Hussain M F Nisar A Majeed K Nawaz and K H BhattildquoEthnomedicinal survey for important plants of Jalalpur JattanDistrict Gujrat Punjab Pakistanrdquo Ethnobotanical Leaflets vol14 pp 807ndash825 2010

[12] M Rahmatullah M A H Mollik A T M A Azam etal ldquoEthnobotanical survey of the Santal tribe residing inThakurgaon District Bangladeshrdquo American-Eurasian Journalof Sustainable Agriculture vol 3 no 4 pp 889ndash898 2009

[13] W Ahmad A Hasan I Ahmad and F Zeenat ldquoEthnomedici-nal plants of Mansoora Malegaonrdquo Hamdard Medicus vol 54pp 29ndash40 2011

[14] S Das M D Choudhury S C Mandal and A D TalukdarldquoTraditional knowledge of ethnomedicinal hepatoprotectiveplants used by certain ethnic communities of Tripura StaterdquoIndian Journal of Fundamental and Applied Life Sciences vol 2pp 84ndash97 2012

[15] B B S Kapoor and M Sharma ldquoEthnomedicinal aspects ofsome medicinal plants of Hanumangarh District of Rajasthanrdquo

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Autoimmune Diseases

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 17

Journal of Pharmaceutical and Biological Sciences vol 1 pp 7ndash92013

[16] A Sharma M S Sharma A Mishra S Sharma B Kumar andA Bhandari ldquoA review on Thar plants used in liver diseasesrdquoInternational Journal of Research in Pharmacy and Chemistryvol 1 pp 224ndash236 2011

[17] V Kumar and P K Singh ldquoEthnomedicinal plants used asantidote for snake-bite and scorpion-sting in Bundelkhand(UP) Indiardquo IOSR Journal of Environmental Science Toxicologyand Food Technology vol 8 no 1 pp 52ndash55 2014

[18] B L Bhellum and S Singh ldquoEthnomedicinal plants of districtSamba of Jammu and Kashmir State (List-II)rdquo InternationalJournal of Scientific and Research Publications vol 2 pp 1ndash82012

[19] M Rahmatullah M A H Mollik A K Paul et al ldquoAcomparative analysis of medicinal plants used to treat gas-trointestinal disorders in two sub-districts of greater Khulnadivision BangladeshrdquoAdvances inNatural andApplied Sciencesvol 4 no 1 pp 22ndash28 2010

[20] A N Korpenwar ldquoEthnomedicinal plants used by the tribalrsquos incure of wounds in Buldhana District (MS) Indiardquo InternationalJournal of Recent Trends in Science and Technology vol 3 pp49ndash53 2012

[21] D Vaidyanathan M S S Senthilkumar and M G BashaldquoStudies on ethnomedicinal plants used by Malayali tribals inKolli Hills of Eastern Ghats Tamil Nadu Indiardquo Asian Journalof Plant Science amp Research vol 3 pp 29ndash45 2013

[22] B C David and G Sudarsanam ldquoEthnomedicinal plant knowl-edge and practice of people of Javadhu hills in TamilnadurdquoAsian Pacific Journal of Tropical Biomedicine vol 1 no 1 ppS79ndashS81 2011

[23] S Sudeesh ldquoEthnomedicinal plants used by Malayaraya tribesof Vannapuram village in Idukki Kerala Indiardquo Indian Journalof Scientific Research and Technology vol 1 pp 7ndash11 2012

[24] K Das and P Duarah ldquoTraditional knowledge of the womenrsquos ofKaibarta community of Assam about the application of phyto-remedies in certain common childhood diseasesrdquo InternationalResearch Journal of Biological Sciences vol 3 pp 57ndash63 2014

[25] M F Nisar S Ismail M Arshad A Majeed and M ArfanldquoEthnomedicinal flora of District Mandi Bahauddin PakistanrdquoMiddle-East Journal of Scientific Research vol 9 pp 233ndash2382011

[26] D F Malan and D F R Neuba ldquoTraditional practices andmedicinal plants use during pregnancy byAnyi-Ndenyewomen(Eastern Cote drsquoIvoire)rdquoAfrican Journal of Reproductive Healthvol 15 no 1 pp 85ndash93 2011

[27] S S Abujam and R K Shah ldquoStudy on the ethnomedicinalsystem of local people of Dibrugarh Assamrdquo InternationalJournal of Pharmaceutical Innovation vol 2 pp 17ndash28 2012

[28] R K Singh and A Singh ldquoWomenrsquos wisdom and indigenoushuman healthcare practicesrdquo Indian Journal of TraditionalKnowledge vol 8 no 2 pp 262ndash269 2009

[29] P Sudhakar and J Shashikanth ldquoEthnomedicinal importanceof some weeds grown in sugarcane crop fields of NizamabadDistrict Andhra Pradesh Indiardquo Life Sciences Leaflets vol 10pp 51ndash55 2012

[30] R Sivaranjani and K Ramakrishnan ldquoTraditional uses ofmedicinal plants in treating skin diseases in NagapattinamDistrict of Tamil Nadu Indiardquo International Research Journalof Pharmacy vol 3 pp 201ndash204 2012

[31] N R Chakraborty and B Duary ldquoUtilization of some weedsas medicine by the local people in Birbhum District of WestBengal Indiardquo International Journal of Bio-resource and StressManagement vol 5 pp 148ndash152 2014

[32] M Panghal V Arya S Yadav S Kumar and J P YadavldquoIndigenous knowledge of medicinal plants used by Saperascommunity of Khetawas Jhajjar District Haryana IndiardquoJournal of Ethnobiology and Ethnomedicine vol 6 article 42010

[33] A V Khan Q U Ahmed M W Khan and A A KhanldquoHerbal cure for poisons and poisonous bites from WesternUttar Pradesh Indiardquo Asian Pacific Journal of Tropical Diseasevol 4 no 1 pp S116ndashS120 2014

[34] L J Landge and A T Kalse ldquoIndigenous herbal medicines usedby tribal people in Satpuda Mountairdquo International ScientificJournal vol 1 pp 65ndash69 2014

[35] S M Simon T S J Norman K Suresh and V RamachandranldquoEthnomedicinal plants used by the Uraly tribes of IdukkiDistrict Kerala which are hitherto unreported in codifiedAyurveda system ofmedicinerdquo International Journal of Researchin Ayurveda and Pharmacy vol 2 pp 469ndash472 2011

[36] N Agnihotri and A K Gupta ldquoFolklore medicines for cuts andwounds in Kalyanpur block of Kanpur District Uttar PradeshIndiardquo PhTechMed vol 2 pp 381ndash386 2013

[37] R C Tewari M Kotecha A K Sharma and P SharmaldquoEthno-medicinal heritage of Chandi Devi Hillrsquos of HaridwarUttarakhandrdquo International Journal of Innovative Research andDevelopment vol 2 pp 233ndash241 2013

[38] K Yesodharan and K A Sujana ldquoStatus of ethnomedicinalplants in the Parambikulam Wildlife Sanctuary Kerala SouthIndiardquo Annals of Forestry vol 15 no 2 pp 322ndash334 2007

[39] B D Vashistha and M Kaur ldquoFloristic and ethno botanicalsurvey of Ambala District Haryanardquo International Journal ofPharma and Bio Sciences vol 4 no 2 pp P353ndashP360 2013

[40] M P Panthi and A G Singh ldquoEthnobotany of ArghakhanchiDistrict Nepal plants used in dermatological and cosmeticdisordersrdquo International Journal of Applied Sciences and Biotech-nology vol 1 no 2 pp 27ndash32 2013

[41] A Kumar S Agarwal A Singh and D Deepak ldquoMedico-botanical study of some weeds growing in Moradabad Districtof Western Uttar Pradesh in Indiardquo Indian Journal of ScientificResearch vol 3 pp 107ndash111 2012

[42] C R Sahu R K Nayak and N K Dhal ldquoTraditional herbalremedies for various diseases used by tribals of Boudh DistrictOdisha India for sustainable developmentrdquo International Jour-nal of Herbal Medicine vol 1 pp 12ndash20 2013

[43] A K Saxena B Singh and K K Anand ldquoHepatoprotectiveeffects of Eclipta alba on subcellular levels in ratsrdquo Journal ofEthnopharmacology vol 40 no 3 pp 155ndash161 1993

[44] B Singh A K Saxena B K Chandan S G Agarwal and KK Anand ldquoIn vivo hepatoprotective activity of active fractionfrom ethanolic extract of Eclipta alba leavesrdquo Indian Journal ofPhysiology and Pharmacology vol 45 no 4 pp 435ndash441 2001

[45] D Manvar M Mishra S Kumar and V N Pandey ldquoIdentifi-cation and evaluation of anti hepatitis C virus phytochemicalsfrom Eclipta albardquo Journal of Ethnopharmacology vol 144 no3 pp 545ndash554 2012

[46] N Tabassum and S S Agrawal ldquoHepatoprotective activity ofEclipta alba Hassk against paracetamol induced hepatocellulardamage in micerdquo JK Practitioner vol 11 no 4 pp 278ndash2802004

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

18 International Scholarly Research Notices

[47] B Singh A K Saxena B K Chandan S G Agarwal M SBhatia and K K Anand ldquoHepatoprotective effect of ethanolicextract of Eclipta alba on experimental liver damage in rats andmicerdquo Phytotherapy Research vol 7 no 2 pp 154ndash158 1993

[48] R Vasuki R Hari S Pandian and G Arumugam ldquoHep-atoprotective action of ethanolic extracts of Eclipta alba andPiper longum linn and their combination on CCL

4induced

hepatotoxicity in ratsrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 4 no 1 pp 455ndash459 2012

[49] K Prabu N Kanchana and A M Sadiq ldquoHepatoprotectiveeffect of Eclipta alba on paracetamol induced liver toxicity inratsrdquo Journal of Microbiology and Biotechnology Research vol 1pp 75ndash79 2011

[50] V K Lal A Kumar P Kumar and K S Yadav ldquoScreening ofleaves and roots of Eclipta alba for hepatoprotective activityrdquoArchives of Applied Science Research vol 2 no 1 pp 86ndash942010

[51] K Arun and U Balasubramanian ldquoComparative study onhepatoprotective activity of Aegle marmelos and Eclipta albaagainst alcohol induced in albino ratsrdquo International Journal ofEnvironmental Science vol 2 pp 389ndash402 2011

[52] S R Parmar P H Vashrambhai and K Kalia ldquoHepatopro-tective activity of some plants extract against paracetamolinduced hepatotoxicity in ratsrdquo Journal of Herbal Medicine andToxicology vol 4 pp 101ndash106 2010

[53] K Kumar A K Katiyar M Swamy Y P Sahni and S KumarldquoHepatoprotective effect of Eclipta alba on experimentallyinduced liver damage in ratsrdquo Indian Journal of VeterinaryPathology vol 37 pp 159ndash163 2013

[54] T Thirumalai E David V Therasa and E K ElumalaildquoRestorative effect of Eclipta alba in CCl

4induced hepatotoxic-

ity in male albino ratsrdquoAsian Pacific Journal of Tropical Diseasevol 1 no 4 pp 304ndash307 2011

[55] K Narayanasamy and V Selvi ldquoHepatoprotective effect ofa polyherbal formulation (Ayush-Liv04) against ethanol andCCl4induced liver damage in ratsrdquo Ancient Science of Life vol

25 no 1 pp 28ndash33 2005[56] M Kavitha S K Karimulla D Kumar S Vinoth Kumar R

Sathish Kumar andM Gurucharan ldquoHepatoprotective activityofa poly herbal extract in carbon tetra chloride intoxicatedhepatotoxicity in male albino ratsrdquo International Journal ofPharma and Bio Sciences vol 2 no 3 pp 307ndash312 2011

[57] R Zafar and B P S Sagar ldquoHepatoprotective and cardiacinhibitory activities of ethanolic extracts from plant leaves andleaf callus of Eclipta albardquo Pharmaceutical Biology vol 38 no 5pp 357ndash361 2000

[58] R K Roy M Thakur and V K Dixit ldquoHair growth promotingactivity of Eclipta alba in male albino ratsrdquo Archives of Derma-tological Research vol 300 no 7 pp 357ndash364 2008

[59] K Datta A T Singh A Mukherjee B Bhat B Ramesh and AC Burman ldquoEclipta alba extract with potential for hair growthpromoting activityrdquo Journal of Ethnopharmacology vol 124 no3 pp 450ndash456 2009

[60] R M Thorat V M Jadhav and V J Kadam ldquoDevelop-ment and evaluation of polyherbal formulations for hairgrowth-promoting activityrdquo International Journal of PharmTechResearch vol 1 no 4 pp 1251ndash1254 2009

[61] S K Bhattacharya K S Satyan and A Chakrabarti ldquoEffect ofTrasina an Ayurvedic herbal formulation on pancreatic isletsuperoxide dismutase activity in hyperglycaemic ratsrdquo IndianJournal of Experimental Biology vol 35 no 3 pp 297ndash299 1997

[62] J Ananthi A Prakasam and K V Pugalendi ldquoAntihyper-glycemic activity ofEclipta alba leaf on alloxan-induced diabeticratsrdquo Yale Journal of Biology and Medicine vol 76 no 1ndash6 pp97ndash102 2003

[63] N Jaiswal V Bhatia S P Srivastava A K Srivastava and AK Tamrakar ldquoAntidiabetic effect of Eclipta alba associated withthe inhibition of 120572-glucosidase and aldose reductaserdquo NaturalProduct Research vol 26 no 24 pp 2363ndash2367 2012

[64] D Kumar R H Gaonkar R Ghosh and B C Pal ldquoBio-assayguided isolation of 120572-glucosidase inhibitory constituents fromEclipta albardquoNatural Product Communications vol 7 no 8 pp989ndash990 2012

[65] P S Pandey K K Upadhyay and D N Pandey ldquoExperimentalevaluation of the analgesic property of Eclipta alba (L) HasskrdquoAncient Science of Life vol 17 pp 36ndash40 1997

[66] L K A M Leal A A G Ferreira G A Bezerra F J A Matosand G S B Viana ldquoAntinociceptive anti-inflammatory andbronchodilator activities of Brazilian medicinal plants contain-ing coumarin a comparative studyrdquo Journal of Ethnopharmacol-ogy vol 70 no 2 pp 151ndash159 2000

[67] M Sawant J C Isaac and S Narayanan ldquoAnalgesic studieson total alkaloids and alcohol extracts of Eclipta alba (Linn)Hasskrdquo Phytotherapy Research vol 18 no 2 pp 111ndash113 2004

[68] S S Kumar T Sivakumar M J Chandrasekar and B SureshldquoEvaluation of anti-Inflammatory activity ofEclipta alba in ratsrdquoAncient Science of Life vol 24 pp 112ndash118 2005

[69] C Lans T Harper K Georges and E Bridgewater ldquoMedicinalplants used for dogs in Trinidad and Tobagordquo PreventiveVeterinary Medicine vol 45 no 3-4 pp 201ndash220 2000

[70] M Kaur and H M Chandola ldquoRole of rasayana in cure andprevention of recurrence of vicharchika (eczema)rdquo Ayu vol 31no 1 pp 33ndash39 2010

[71] C-F Chan W-Y Huang H-Y Guo and B R Wang ldquoPotentantioxidative and UVB protective effect of water extract ofEclipta prostrata Lrdquo The Scientific World Journal vol 2014Article ID 759039 8 pages 2014

[72] V DThakur and S AMengi ldquoNeuropharmacological profile ofEclipta alba (Linn) Hasskrdquo Journal of Ethnopharmacology vol102 no 1 pp 23ndash31 2005

[73] O Banji D Banji A R Annamalai and R ManavalanldquoInvestigation on the effect of Eclipta alba on animal modelsof learning and memoryrdquo Indian Journal of Physiology andPharmacology vol 51 no 3 pp 274ndash278 2007

[74] O J F Lobo D Banji A R Annamalai and R ManavalanldquoEvaluation of antiaggressive activity of Eclipta alba in exper-imental animalsrdquo Pakistan Journal of Pharmaceutical Sciencesvol 21 no 2 pp 195ndash199 2008

[75] M Bhaskar and M Chintamaneni ldquoWithania somnifera andEclipta alba ameliorate oxidative stress induced mitochondrialdysfunction in an animal model of Alzheimerrsquos diseaserdquo TheAmerican Journal of Phytomedicine and Clinical Therapeuticsvol 2 pp 140ndash152 2014

[76] G Kaur R Tuli and M Chintamaneni ldquoAntioxidant potentialof methanolic and hydrolyzed extracts of Eclipta albardquo Pharma-cologyonline vol 2 pp 947ndash956 2009

[77] N Uddin A Rahman N U Ahmed S Rana R Akter andA M M A Chowdhury ldquoAntioxidant cytotoxic and antimi-crobial properties of Eclipta alba ethanol extractrdquo InternationalJournal of Biological and Medical Research vol 1 no 4 pp 341ndash346 2010

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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ToxinsJournal of

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 19

[78] Swati S Bedi and Tanuja ldquoIn vitro antioxidant potentialand phytochemical screening of Eclipta albardquo Asian Journal ofExperimental Biological Sciences vol 3 no 4 pp 785ndash789 2012

[79] S Chandan S Umesha and V Balamurugan ldquoAntileptospiralantioxidant and DNA damaging properties of Eclipta alba andPhyllanthus amarusrdquo Open Access Scientific Reports vol 1 pp231ndash238 2012

[80] A Baldi R Gupta and M S Panwar ldquoEvaluation of in-vitroantioxidant activity of Eclipta albardquo International Journal ofPharmaceutical and Biological Archive vol 2 pp 767ndash771 2011

[81] S Karthikumar K Vigneswari and K Jegatheesan ldquoScreeningof antibacterial and antioxidant activities of leaves of Ecliptaprostrata (L)rdquo Scientific Research and Essay vol 2 no 4 pp 101ndash104 2007

[82] K P Mansoorali T Prakash D Kotresha K Prabhu and NRama Rao ldquoCerebroprotective effect of Eclipta alba againstglobal model of cerebral ischemia induced oxidative stress inratsrdquo Phytomedicine vol 19 no 12 pp 1108ndash1116 2012

[83] M Panghal V Kaushal and J P Yadav ldquoIn vitro antimicrobialactivity of ten medicinal plants against clinical isolates of oralcancer casesrdquo Annals of Clinical Microbiology and Antimicro-bials vol 10 article 21 2011

[84] M K Pandey G N Singh R K Sharma and S LataldquoAntibacterial activity of Eclipta alba (L) hasskrdquo Journal ofApplied Pharmaceutical Science vol 1 no 7 pp 104ndash107 2011

[85] J Bakht A Islam and M Shafi ldquoAntimicrobial potentials ofEclipta alba by well diffusion methodrdquo Pakistan Journal ofBotany vol 43 pp 169ndash174 2011

[86] P S Sandhu K Kaur V Ahmad et al ldquoScreening of antimi-crobial activity of aqueous extracts of leaves flower and stemof Eclipta albardquo International Journal of Drug Development andResearch vol 4 no 4 pp 142ndash147 2012

[87] M K Peraman P Ramalingam and B J N N Sai ldquoAnti-inflammatory and antimicrobial activities of the extracts ofEclipta alba leavesrdquo European Journal of Experimental Biologyvol 1 pp 172ndash177 2011

[88] M Borkataky B B Kakoty and L R Saikia ldquoProximateanalysis and antimicrobial activity of Eclipta alba (L) Hasskmdashatraditionally used herbrdquo International Journal of Pharmacy andPharmaceutical Sciences vol 5 no 1 pp 149ndash154 2013

[89] M I S Saggoo R Kaur and R C Gupta ldquoComparison ofantibacterial activity of three morphotypes of medicinal herbEclipta alba (L) Hasskrdquo Der Pharmacia Lettre vol 2 pp 200ndash207 2010

[90] N Saraswathy and P M Kumaran ldquoEvaluation of aque-ous extract of Eclipta alba leaves for preservation potentialagainst Fusarium speciesrdquo The American Journal of PharmTechResearch vol 2 pp 645ndash649 2012

[91] S Dalal S K Kataria K V Sastry and S V S Rana ldquoPhy-tochemical screening of methanolic extract and antibacterialactivity of active principles of hepatoprotective herb Ecliptaalbardquo Ethnobotanical Leaflets vol 14 pp 248ndash258 2010

[92] A Ray P Bharali and B K Konwar ldquoMode of antibacterialactivity of eclalbasaponin isolated from Eclipta albardquo AppliedBiochemistry and Biotechnology vol 171 no 8 pp 2003ndash20192013

[93] B Saroj A Shashank S Shirshat Mahendra J Suryaji L SPatil and R A Deshmukh ldquoAnti-malarial activity of Ecliptaalba against Plasmodium berghei infection in micerdquo Journal ofCommunicable Diseases vol 39 no 2 pp 91ndash94 2007

[94] M Govindarajan ldquoEvaluation of indigenous plant extractsagainst the malarial vector Anopheles stephensi (Liston)(Diptera Culicidae)rdquo Parasitology Research vol 109 no 1 pp93ndash103 2011

[95] M Govindarajan and P Karuppannan ldquoMosquito larvicidaland ovicidal properties of Eclipta alba (L) Hassk (Asteraceae)against chikungunya vector Aedes aegypti (Linn) (DipteraCulicidae)rdquoAsian Pacific Journal of TropicalMedicine vol 4 no1 pp 24ndash28 2011

[96] M Govindarajan and R Sivakumar ldquoAdulticidal and repellentproperties of indigenous plant extracts against Culex quinque-fasciatus and Aedes aegypti (Diptera Culicidae)rdquo ParasitologyResearch vol 110 no 5 pp 1607ndash1620 2012

[97] M Govindarajan and R Sivakumar ldquoMosquito adulticidal andrepellent activities of botanical extracts against malarial vectorAnopheles stephensi Liston (Diptera Culicidae)rdquo Asian PacificJournal of Tropical Medicine vol 4 no 12 pp 941ndash947 2011

[98] V Rangineni D Sharada and S Saxena ldquoDiuretic hypotensiveand hypocholesterolemic effects of Eclipta alba in mild hyper-tensive subjects a pilot studyrdquo Journal ofMedicinal Food vol 10no 1 pp 143ndash148 2007

[99] DChristybapitaMDivyagnaneswari andRDMichael ldquoOraladministration of Eclipta alba leaf aqueous extract enhancesthe non-specific immune responses and disease resistance ofOreochromis mossambicusrdquo Fish and Shellfish Immunology vol23 no 4 pp 840ndash852 2007

[100] M G Jayathirtha and S HMishra ldquoPreliminary immunomod-ulatory activities of methanol extracts of Eclipta alba andCentella asiaticardquo Phytomedicine vol 11 no 4 pp 361ndash3652004

[101] M F Shaikh J Sancheti and S Sathaye ldquoPhytochemical andpharmacological investigations of Eclipta alba (Linn) Hassakleaves for antiepileptic activityrdquo International Journal of Phar-macy and Pharmaceutical Sciences vol 4 no 4 pp 319ndash3232012

[102] M F Shaikh J Sancheti and S Sathaye ldquoEffect of Eclipta albaon acute seizure models A GABA

119860-mediated effectrdquo Indian

Journal of Pharmaceutical Sciences vol 75 no 3 pp 380ndash3842013

[103] F Loup H-G Wieser Y Yonekawa A Aguzzi and J-MFritschy ldquoSelective alterations in GABA

119860receptor subtypes in

human temporal lobe epilepsyrdquoThe Journal of Neuroscience vol20 no 14 pp 5401ndash5419 2000

[104] E S C Pocas D V S Lopes A J M da Silva et al ldquoStructure-activity relationship of wedelolactone analogues structuralrequirements for inhibition of Na+K+-ATPase and binding tothe central benzodiazepine receptorrdquo Bioorganic and MedicinalChemistry vol 14 no 23 pp 7962ndash7966 2006

[105] K Dirscherl M Karlstetter S Ebert et al ldquoLuteolin triggersglobal changes in the microglial transcriptome leading toa unique anti-inflammatory and neuroprotective phenotyperdquoJournal of Neuroinflammation vol 7 article 3 2010

[106] S Mishra M Jena and S S Mishra ldquoEvaluation of anticonvul-sant and muscle relaxant activities of Eclipta alba using animalmodelsrdquo IndoAmerican Journal of Pharmaceutical Research vol4 pp 1397ndash1401 2014

[107] M Jena and S Mishra ldquoSedative and antianxiety activity ofethanolic extract of Eclipta alba in albino ratsrdquo InternationalJournal of Pharma and Bio Sciences vol 4 no 4 pp 1ndash8 2013

[108] D Sivaraman and P Muralidaran ldquoCNS depressant andantiepileptic activities of the methanol extract of the leaves of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

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The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

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Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

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Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

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Pharmaceutics

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MEDIATORSINFLAMMATION

of

20 International Scholarly Research Notices

Ipomoea aquatica forskrdquo E-Journal of Chemistry vol 7 no 4pp 1555ndash1561 2010

[109] L C Diogo R S Fernandes S Marcussi et al ldquoInhibitionof snake venoms and phospholipases A

2by Extracts from

native and genetically modified Eclipta alba isolation of activecoumestansrdquo Basic and Clinical Pharmacology and Toxicologyvol 104 no 4 pp 293ndash299 2009

[110] H Chaudhary V Dhuna J Singh S S Kamboj and S SeshadrildquoEvaluation of hydro-alcoholic extract of Eclipta alba for itsanticancer potential an in vitro studyrdquo Journal of Ethnopharma-cology vol 136 no 2 pp 363ndash367 2011

[111] H Chaudhary P K Jena and S Seshadri ldquoEvaluation of hydro-alcoholic extract of Eclipta alba for its multidrug resistancereversal potential an in vitro studyrdquo Nutrition and Cancer vol65 no 5 pp 775ndash780 2013

[112] K Lirdprapamongkol J-P Kramb D Chokchaichamnankit etal ldquoJuice of Eclipta prostrata inhibits cell migration in vitro andexhibits anti-angiogenic activity in vivordquo In Vivo vol 22 no 3pp 363ndash368 2008

[113] N Chauhan D Singh and R M Painuli ldquoScreening ofbioprotective properties and phytochemical analysis of variousextracts of Eclipta alba whole plantrdquo International Journal ofPharmacy and Pharmaceutical Sciences vol 4 no 2 pp 554ndash560 2012

[114] Y H Siddique G Ara T Beg M Faisal and M AfzalldquoProtective role ofEclipta alba L extract against ethinylestradiolinduced genotoxic damage in cultured human lymphocytesrdquoAlternative Medicine Studies vol 1 pp 14ndash17 2011

[115] R B Desireddy G N Sowjanya K L L Reddy and TSowjanya ldquoScreening of Eclipta alba extracts for anticanceractivityrdquo International Journal of Research and Development inPharmacy amp Life Sciences vol 1 pp 203ndash205 2012

[116] M K Lee N R Ha H Yang S H Sung G H Kim and YC Kim ldquoAntiproliferative activity of triterpenoids from Ecliptaprostrata on hepatic stellate cellsrdquo Phytomedicine vol 15 no 9pp 775ndash780 2008

[117] S P Kumar B S Kumar V R Chandana M Vijaykumar S KOjha and M E Bavani ldquoAntisecretory and antiulcer activitiesof Eclipta alba Linn In ratsrdquo in Proceedings of the 5th WorldAyurveda Congress Oral Presentation Abstract No OA0103Bhopal India December 2012

[118] A Banerjee N Shrivastava A Kothari H Padh and MNivsarkar ldquoAntiulcer activity of methanol extract of Ecliptaalbardquo Indian Journal of Pharmaceutical Sciences vol 67 no 2pp 165ndash168 2005

[119] S C Ghule S R Chaudhari and M J Chavan ldquoAnthelminticpotential ofEclipta alba (L)Hassk againstPheretima posthumardquoInternational Journal of Pharmacy and Pharmaceutical Sciencesvol 3 no 1 pp 143ndash144 2011

[120] S D Bhinge M G Hogade C Chavan M Kumbhar andV Chature ldquoIn vitro anthelmintic activity of herb extract ofEclipta prostrate L against Pheretima posthumardquo Asian Journalof Pharmaceutical and Clinical Research vol 3 no 3 pp 229ndash230 2010

[121] HWagner and B Fessler ldquoIn vitro 5-lipoxygenase inhibition byEclipta alba extracts and the coumestan derivative wedelolac-tonerdquo Planta Medica vol 5 pp 374ndash377 1986

[122] E S Silverman and J M Drazen ldquoThe biology of 5-lipoxygenase Function structure and regulatorymechanismsrdquoProceedings of the Association of American Physicians vol 111no 6 pp 525ndash536 1999

[123] S M Wong S Antus A Gottsegen et al ldquoWedelolactone andcoumestan derivatives as new antihepatotoxic and antiphlogis-tic principlesrdquo Arzneimittel-Forschung vol 38 no 5 pp 661ndash665 1988

[124] W B Mors M C Do Nascimento J P Parente M H DaSilva P A Melo and G Suarez-Kurtz ldquoNeutralization oflethal and myotoxic activities of south american rattlesnakevenomby extracts and constituents of the plant Eclipta prostrata(Asteraceae)rdquo Toxicon vol 27 no 9 pp 1003ndash1009 1989

[125] P A Melo M C D Nascimento W B Mors and G Suarez-Kurtz ldquoInhibition of the myotoxic and hemorrhagic activitiesof crotalid venoms byEclipta prostrata (Asteraceae) extracts andconstituentsrdquo Toxicon vol 32 no 5 pp 595ndash603 1994

[126] P A Melo and C L Ownby ldquoAbility of wedelolactone heparinand para-bromophenacyl bromide to antagonize the myotoxiceffects of two crotaline venoms and their PLA2 myotoxinsrdquoToxicon vol 37 no 1 pp 199ndash215 1999

[127] M Kobori Z Yang D Gong et al ldquoWedelolactone suppressesLPS-induced caspase-11 expression by directly inhibiting theIKK complexrdquo Cell Death and Differentiation vol 11 no 1 pp123ndash130 2004

[128] F Yuan J Chen P P Sun S Guan and J Xu ldquoWedelolactoneinhibits LPS-induced pro-inflammation via NF-120581B Pathway inRAW 2647 cellsrdquo Journal of Biomedical Science vol 20 no 1article 84 2013

[129] S Tewtrakul S Subhadhirasakul S Cheenpracha and C Kar-alai ldquoHIV-1 protease and HIV-1 integrase inhibitory substancesfrom Eclipta prostratardquo Phytotherapy Research vol 21 no 11 pp1092ndash1095 2007

[130] F-M Lin L-R Chen E-H Lin et al ldquoCompounds fromWedelia chinensis synergistically suppress androgen activity andgrowth in prostate cancer cellsrdquo Carcinogenesis vol 28 no 12pp 2521ndash2529 2007

[131] P Benes L Knopfova F Trcka et al ldquoInhibition of topoiso-merase II120572 novel function of wedelolactonerdquo Cancer Lettersvol 303 no 1 pp 29ndash38 2011

[132] W M Huston S Gloeckl L de Boer K W Beagley andP Timms ldquoApoptosis is induced in Chlamydia trachomatis-infected HEp-2 cells by the addition of a combination innateimmune activation compounds and the inhibitor wedelolac-tonerdquo The American Journal of Reproductive Immunology vol65 no 5 pp 460ndash465 2011

[133] H Deng and Y Fang ldquoAnti-inflammatory gallic acid andwedelolactone are G protein-coupled receptor-35 agonistsrdquoPharmacology vol 89 no 3-4 pp 211ndash219 2012

[134] S-W Qian X Li Y-Y Zhang et al ldquoCharacterization ofadipocyte differentiation from human mesenchymal stem cellsin bonemarrowrdquoBMCDevelopmental Biology vol 10 article 472010

[135] S Lim H-J Jang E H Park et al ldquoWedelolactone inhibitsadipogenesis through the ERK pathway in human adiposetissue-derived mesenchymal stem cellsrdquo Journal of CellularBiochemistry vol 113 no 11 pp 3436ndash3445 2012

[136] S Sarveswaran S C Gautam and J Ghosh ldquoWedelolac-tone a medicinal plant-derived coumestan induces caspase-dependent apoptosis in prostate cancer cells via downregulationof PKC120576without inhibiting Aktrdquo International Journal of Oncol-ogy vol 41 no 6 pp 2191ndash2199 2012

[137] D N Dhanasekaran and E P Reddy ldquoJNK signaling inapoptosisrdquo Oncogene vol 27 no 48 pp 6245ndash6251 2008

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

International Scholarly Research Notices 21

[138] A G Porter and R U Janicke ldquoEmerging roles of caspase-3 inapoptosisrdquo Cell Death and Differentiation vol 6 no 2 pp 99ndash104 1999

[139] H Okhrimenko W Lu C Xiang N Hamburger G Kaz-imirsky and C Brodie ldquoProtein kinase C-120576 regulates theapoptosis and survival of glioma cellsrdquo Cancer Research vol 65no 16 pp 7301ndash7309 2005

[140] Z Chen X Sun S Shen et al ldquoWedelolactone a naturallyoccurring coumestan enhances interferon-120574 signaling throughinhibiting STAT1 protein dephosphorylationrdquo Journal of Biolog-ical Chemistry vol 288 no 20 pp 14417ndash14427 2013

[141] A Stephanou and D S Latchman ldquoSTAT-1 a novel regulator ofapoptosisrdquo International Journal of Experimental Pathology vol84 no 6 pp 239ndash244 2003

[142] Y Xia J Chen Y Cao et al ldquoWedelolactone exhibits anti-fibrotic effects on human hepatic stellate cell line LX-2rdquo Euro-pean Journal of Pharmacology vol 714 no 1ndash3 pp 105ndash111 2013

[143] Q M Liu H Y Zhao X K Zhong and J G Jiang ldquoEcliptaprostrata L phytochemicals Isolation structure elucidationand their antitumor activityrdquo Food andChemical Toxicology vol50 no 11 pp 4016ndash4022 2012

[144] S Ryu J-S Shin J Y Jung et al ldquoEchinocystic acid isolatedfrom Eclipta prostrata suppresses Lipopolysaccharide-inducediNOS TNF- 120572 and IL-6 expressions via NF-120581 B inactivationin RAW 2647 macrophagesrdquo Planta Medica vol 79 no 12 pp1031ndash1037 2013

[145] G Kweifio-Okai and T A Macrides ldquoAntilipoxygenase activityof amyrin triterpenesrdquo Research Communications in ChemicalPathology and Pharmacology vol 78 no 3 pp 367ndash372 1992

[146] G Kweifio-Okai D Bird P Eu A R Carroll R Ambrose andB Field ldquoEffect of 120572-amyrin palmitate on adjuvant arthritisrdquoDrugs under Experimental and Clinical Research vol 20 no 1pp 1ndash5 1994

[147] G Kweifio-Okai F DeMunk B A Rumble T AMacrides andM Cropley ldquoAntiarthritic mechanisms of amyrin triterpenesrdquoResearch Communications in Molecular Pathology and Pharma-cology vol 85 no 1 pp 45ndash55 1994

[148] M F Otuki J Ferreira F V Lima et al ldquoAntinociceptiveproperties of mixture of 120572-amyrin and 120573-amyrin triterpenesevidence for participation of protein kinase C and proteinkinase A pathwaysrdquo Journal of Pharmacology and ExperimentalTherapeutics vol 313 no 1 pp 310ndash318 2005

[149] M F Otuki F Vieira-Lima A Malheiros R A Yunes and J BCalixto ldquoTopical antiinflammatory effects of the ether extractfrom Protium kleinii and 120572-amyrin pentacyclic triterpenerdquoEuropean Journal of Pharmacology vol 507 no 1ndash3 pp 253ndash259 2005

[150] R Medeiros M F Otuki M C W Avellar and J B Cal-ixto ldquoMechanisms underlying the inhibitory actions of thepentacyclic triterpene 120572-amyrin in the mouse skin inflamma-tion induced by phorbol ester 12-O-tetradecanoylphorbol-13-acetaterdquo European Journal of Pharmacology vol 559 no 2-3 pp227ndash235 2007

[151] C M Melo T C Morais A R Tome et al ldquoAnti-inflammatoryeffect of 120572120573-amyrin a triterpene from Protium heptaphyllumon cerulein-induced acute pancreatitis in micerdquo InflammationResearch vol 60 no 7 pp 673ndash681 2011

[152] C M Melo K M M B Carvalho J C de Sousa Neves etal ldquo120572120573-amyrin a natural triterpenoid ameliorates L-arginine-induced acute pancreatitis in ratsrdquo World Journal of Gastroen-terology vol 16 no 34 pp 4272ndash4280 2010

[153] F A Oliveira C L S Costa M H Chaves et al ldquoAttenuationof capsaicin-induced acute and visceral nociceptive pain by120572- and 120573-amyrin a triterpene mixture isolated from Protiumheptaphyllum resin in micerdquo Life Sciences vol 77 no 23 pp2942ndash2952 2005

[154] R C P Lima Jr F A Oliveira L A Gurgel et al ldquoAttenuationof visceral nociception by 120572- and 120573- amyrin a triterpenoidmixture isolated from the resin of Protium heptaphyllum inmicerdquo Planta Medica vol 72 no 1 pp 34ndash39 2006

[155] C E Vitor C P Figueiredo D B Hara A F Bento T LMazzuco and J B Calixto ldquoTherapeutic action and underlyingmechanisms of a combination of two pentacyclic triterpenes120572and 120573-amyrin in a mouse model of colitisrdquo British Journal ofPharmacology vol 157 no 6 pp 1034ndash1044 2009

[156] I Matos A F Bento R Marcon R F Claudino and J BCalixto ldquoPreventive and therapeutic oral administration of thepentacyclic triterpene 120572120573-amyrin ameliorates dextran sulfatesodium-induced colitis in mice the relevance of cannabinoidsystemrdquo Molecular Immunology vol 54 no 3-4 pp 482ndash4922013

[157] N Ali ldquoBrine shrimp cytotoxicity of crude methanol extractand antispasmodic activity of 120572-amyrin acetate from Tylophorahirsuta Wallrdquo BMC Complementary and Alternative Medicinevol 13 article 135 2013

[158] F A Santos J T Frota B R Arruda et al ldquoAntihyperglycemicand hypolipidemic effects of120572120573-amyrin a triterpenoidmixturefrom Protium heptaphyllum in micerdquo Lipids in Health andDisease vol 11 article 98 2012

[159] A B Singh D K Yadav R Maurya and A K SrivastavaldquoAntihyperglycaemic activity of 120572-amyrin acetate in rats anddbdb micerdquo Natural Product Research vol 23 no 9 pp 876ndash882 2009

[160] E Biskup M Golebiowski R Gniadecki P Stepnowski and ELojkowska ldquoTriterpenoid 120572-amyrin stimulates proliferation ofhuman keratinocytes but does not protect them against UVBdamagerdquo Acta Biochimica Polonica vol 59 no 2 pp 255ndash2602012

[161] K Chenniappan and M Kadarkari ldquoAdult mortality and bloodfeeding behavioral effects of 120572-amyrin acetate a novel bioactivecompound on in vivo exposed females of Anopheles stephensiliston (Diptera Culicidae)rdquo Parasitology Research vol 110 no6 pp 2117ndash2124 2012

[162] G F Aragao L M V Carneiro A P F Junior et al ldquoApossible mechanism for anxiolytic and antidepressant effects of120572- and 120573-amyrin from Protium heptaphyllum (Aubl) MarchrdquoPharmacology Biochemistry and Behavior vol 85 no 4 pp 827ndash834 2006

[163] F A Oliveira M H Chaves F R C Almeida et alldquoProtective effect of 120572- And 120573-amyrin a triterpene mixturefrom Protium heptaphyllum (Aubl) March trunk wood resinagainst acetaminophen-induced liver injury in micerdquo Journal ofEthnopharmacology vol 98 no 1-2 pp 103ndash108 2005

[164] F A Oliveira G M Vieira Jr M H Chaves et al ldquoGastropro-tective effect of the mixture of 120572- and 120573-amyrin from Protiumheptaphyllum role of capsaicin-sensitive primary afferent neu-ronsrdquo Planta Medica vol 70 no 8 pp 780ndash782 2004

[165] F A Oliveira R C P Lima-Junior W M Cordeiro et alldquoPentacyclic triterpenoids 120572120573-amyrins suppress the scratch-ing behavior in a mouse model of pruritusrdquo PharmacologyBiochemistry and Behavior vol 78 no 4 pp 719ndash725 2004

[166] J M Castellano A Guinda T Delgado M Rada and JA Cayuela ldquoBiochemical basis of the antidiabetic activity of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

22 International Scholarly Research Notices

oleanolic acid and related pentacyclic triterpenesrdquoDiabetes vol62 no 6 pp 1791ndash1799 2013

[167] K N Lewis J Mele J D Hayes and R Buffenstein ldquoNrf2a guardian of healthspan and gatekeeper of species longevityrdquoIntegrative and Comparative Biology vol 50 no 5 pp 829ndash8432010

[168] M K Shanmugam X Dai A P Kumar B K Tan G Sethiand A Bishayee ldquoOleanolic acid and its synthetic derivativesfor the prevention and therapy of cancer preclinical and clinicalevidencerdquo Cancer Letters vol 346 pp 206ndash216 2014

[169] Y Ikeda A Murakami and H Ohigashi ldquoUrsolic acid an anti-and pro-inflammatory triterpenoidrdquo Molecular Nutrition andFood Research vol 52 no 1 pp 26ndash42 2008

[170] N Sultana ldquoClinically useful anticancer antitumor and anti-wrinkle agent ursolic acid and related derivatives as medici-nally important natural productrdquo Journal of Enzyme Inhibitionand Medicinal Chemistry vol 26 no 5 pp 616ndash642 2011

[171] J Liu ldquoPharmacology of oleanolic acid and ursolic acidrdquo Journalof Ethnopharmacology vol 49 no 2 pp 57ndash68 1995

[172] K-Y Yoo and S-Y Park ldquoTerpenoids as potential anti-Alzheimerrsquos disease therapeuticsrdquo Molecules vol 17 no 3 pp3524ndash3538 2012

[173] L-L Zang B-N Wu Y Lin J Wang L Fu and Z-Y TangldquoResearch progress of ursolic acids anti-tumor actionsrdquoChineseJournal of Integrative Medicine vol 20 no 1 pp 72ndash79 2014

[174] X Chen G A Muller M Quaas et al ldquoThe forkhead tran-scription factor FOXM1 controls cell cycle-dependent geneexpression through an atypical chromatin bindingmechanismrdquoMolecular and Cellular Biology vol 33 no 2 pp 227ndash236 2013

[175] C Yang H Chen L Yu et al ldquoInhibition of FOXM1 transcrip-tion factor suppresses cell proliferation and tumor growth ofbreast cancerrdquo Cancer Gene Therapy vol 20 no 2 pp 117ndash1242013

[176] G Seelinger I Merfort and C M Schempp ldquoAnti-oxidantanti-inflammatory and anti-allergic activities of luteolinrdquoPlanta Medica vol 74 no 14 pp 1667ndash1677 2008

[177] G Seelinger I Merfort U Wolfle and C M Schempp ldquoAnti-carcinogenic effects of the flavonoid luteolinrdquoMolecules vol 13no 10 pp 2628ndash2651 2008

[178] Y Lin R Shi X Wang and H-M Shen ldquoLuteolin a flavonoidwith potential for cancer prevention and therapyrdquo CurrentCancer Drug Targets vol 8 no 7 pp 634ndash646 2008

[179] M Lopez-Lazaro ldquoDistribution and biological activities of theflavonoid luteolinrdquoMini-Reviews inMedicinal Chemistry vol 9no 1 pp 31ndash59 2009

[180] X Tongda D Li and D Jiang ldquoTargeting cell signaling andapoptotic pathways by luteolin cardioprotective role in ratcardiomyocytes following ischemiareperfusionrdquoNutrients vol4 no 12 pp 2008ndash2019 2012

[181] D Patel S Shukla and S Gupta ldquoApigenin and cancerchemoprevention progress potential and promise (review)rdquoInternational Journal of Oncology vol 30 no 1 pp 233ndash2452007

[182] S Shukla and S Gupta ldquoApigenin a promising molecule forcancer preventionrdquo Pharmaceutical Research vol 27 no 6 pp962ndash978 2010

[183] M Piantelli C Rossi M Iezzi et al ldquoFlavonoids inhibitmelanoma lung metastasis by impairing tumor cells endothe-lium interactionsrdquo Journal of Cellular Physiology vol 207 no 1pp 23ndash29 2006

[184] L Wang L Kuang J A Hitron et al ldquoApigenin suppressesmigration and invasion of transformed cells through down-regulation of C-X-C chemokine receptor 4 expressionrdquo Toxicol-ogy and Applied Pharmacology vol 272 no 1 pp 108ndash116 2013

[185] E C Lefort and J Blay ldquoApigenin and its impact on gastroin-testinal cancersrdquoMolecular Nutrition and Food Research vol 57no 1 pp 126ndash144 2013

[186] Y-Y Bao S-H Zhou J Fan and Q-Y Wang ldquoAnticancermechanism of apigenin and the implications of GLUT-1 expres-sion in head and neck cancersrdquo Future Oncology vol 9 no 9pp 1353ndash1364 2013

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PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Submit your manuscripts athttpwwwhindawicom

PainResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom

Volume 2014

ToxinsJournal of

VaccinesJournal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AntibioticsInternational Journal of

ToxicologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Drug DeliveryJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Advances in Pharmacological Sciences

Tropical MedicineJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

AddictionJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

Emergency Medicine InternationalHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Autoimmune Diseases

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Anesthesiology Research and Practice

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Pharmaceutics

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of