10
Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 273712, 9 pages http://dx.doi.org/10.1155/2013/273712 Review Article Loranthus micranthus Linn.: Biological Activities and Phytochemistry Soheil Zorofchian Moghadamtousi, 1 Maryam Hajrezaei, 2 Habsah Abdul Kadir, 1 and Keivan Zandi 3 1 Biomolecular Research Group, Biochemistry Program, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia 2 Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia 3 Department of Medical Microbiology, Tropical Infectious Disease Research and Education Center (TIDREC), Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia Correspondence should be addressed to Keivan Zandi; [email protected] Received 29 April 2013; Accepted 4 August 2013 Academic Editor: Mohamad Fawzi Mahomoodally Copyright © 2013 Soheil Zorofchian Moghadamtousi et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Loranthus micranthus Linn. is a medicinal plant from the Loranthaceae family commonly known as an eastern Nigeria species of the African mistletoe and is widely used in folkloric medicine to cure various ailments and diseases. It is semiparasitic plant because of growing on various host trees and shrubs and absorbing mineral nutrition and water from respective host. Hence, the phytochemicals and biological activities of L. micranthus demonstrated strong host and harvesting period dependency. e leaves have been proved to possess immunomodulatory, antidiabetic, antimicrobial, antihypertensive, antioxidant, antidiarrhoeal, and hypolipidemic activities. is review summarizes the information and findings concerning the current knowledge on the biological activities, pharmacological properties, toxicity, and chemical constituents of Loranthus micranthus. 1. Introduction Loranthus micranthus (L. micranthus) as member of the Loranthaceae family is the eastern Nigeria species of the African mistletoe. Mistletoes are the semiparasitic plants because they normally grow on various host trees and shrubs and they are dependent on their respective host for mineral nutrition and water, although they produce their own carbohydrates through photosynthesis [1]. Mistletoe was described as “an all purpose herb” due to its rich traditional uses and it has been widely used in ethnomedicine for var- ious purposes, including antihypertensive, anticancer, anti- spasmodic, and antidiabetic, and for treatment of epilepsy, headache, infertility, menopausal syndrome and rheumatism [2, 3]. Previous studies demonstrated that composition and hence biological activities of mistletoe are dependent on harvesting period and host tree species [47]. Nigeria has wide distribution of mistletoes with different local names that depend on the area where they occur. Loranthus micranthus represents Eastern Nigeria mistletoes that mostly grow in the southeastern region of the country. It grows on various host trees including Persia americana, Baphia nitida, Kola acuminata, Pentaclethra macrophylla, and Azadirachta indica [8, 9]. L. micranthus has been widely used in folk medicine as antimicrobial, antihypertensive, anticancer, and antidia- betic agent, for treatment of headache, infertility, epilepsy, cardiovascular diseases, menopausal syndrome, agglutina- tion, and rheumatism, and also in conditions that generally require immunomodulatory. Some of these ethnomedicinal uses have already been supported and acclaimed by several

Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

  • Upload
    others

  • View
    1

  • Download
    0

Embed Size (px)

Citation preview

Page 1: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2013 Article ID 273712 9 pageshttpdxdoiorg1011552013273712

Review ArticleLoranthus micranthus Linn BiologicalActivities and Phytochemistry

Soheil Zorofchian Moghadamtousi1 Maryam Hajrezaei2

Habsah Abdul Kadir1 and Keivan Zandi3

1 Biomolecular Research Group Biochemistry Program Institute of Biological Sciences Faculty of Science University of Malaya50603 Kuala Lumpur Malaysia

2 Department of Molecular Medicine Faculty of Medicine University of Malaya 50603 Kuala Lumpur Malaysia3 Department of Medical Microbiology Tropical Infectious Disease Research and Education Center (TIDREC) Faculty of MedicineUniversity of Malaya 50603 Kuala Lumpur Malaysia

Correspondence should be addressed to Keivan Zandi keivanumedumy

Received 29 April 2013 Accepted 4 August 2013

Academic Editor Mohamad Fawzi Mahomoodally

Copyright copy 2013 Soheil Zorofchian Moghadamtousi et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

Loranthus micranthus Linn is a medicinal plant from the Loranthaceae family commonly known as an eastern Nigeria speciesof the African mistletoe and is widely used in folkloric medicine to cure various ailments and diseases It is semiparasitic plantbecause of growing on various host trees and shrubs and absorbing mineral nutrition and water from respective host Hence thephytochemicals and biological activities of L micranthus demonstrated strong host and harvesting period dependency The leaveshave been proved to possess immunomodulatory antidiabetic antimicrobial antihypertensive antioxidant antidiarrhoeal andhypolipidemic activitiesThis review summarizes the information and findings concerning the current knowledge on the biologicalactivities pharmacological properties toxicity and chemical constituents of Loranthus micranthus

1 Introduction

Loranthus micranthus (L micranthus) as member of theLoranthaceae family is the eastern Nigeria species of theAfrican mistletoe Mistletoes are the semiparasitic plantsbecause they normally grow on various host trees andshrubs and they are dependent on their respective host formineral nutrition and water although they produce theirown carbohydrates through photosynthesis [1]Mistletoe wasdescribed as ldquoan all purpose herbrdquo due to its rich traditionaluses and it has been widely used in ethnomedicine for var-ious purposes including antihypertensive anticancer anti-spasmodic and antidiabetic and for treatment of epilepsyheadache infertility menopausal syndrome and rheumatism[2 3] Previous studies demonstrated that composition and

hence biological activities of mistletoe are dependent onharvesting period and host tree species [4ndash7] Nigeria haswide distribution ofmistletoes with different local names thatdepend on the area where they occur Loranthus micranthusrepresents Eastern Nigeria mistletoes that mostly grow inthe southeastern region of the country It grows on varioushost trees including Persia americana Baphia nitida Kolaacuminata Pentaclethra macrophylla and Azadirachta indica[8 9] L micranthus has been widely used in folk medicineas antimicrobial antihypertensive anticancer and antidia-betic agent for treatment of headache infertility epilepsycardiovascular diseases menopausal syndrome agglutina-tion and rheumatism and also in conditions that generallyrequire immunomodulatory Some of these ethnomedicinaluses have already been supported and acclaimed by several

2 Evidence-Based Complementary and Alternative Medicine

investigations [1 2 10 11] In Nigeria and South AfricaL micranthus has been widely used as ethnomedicine fortreatment of hypertension diabetes and schizophrenia andas an immune system booster [10]

2 Phytochemistry

Extensive phytochemical evaluations of L micranthusextracts demonstrated the presence of various phyto-constituents and compounds Crude methanolic extractfrom leaves of L micranthus harvested from P americanawasfound to possess terpenoids steroids oils proteins resinsflavonoids tannins saponins alkaloids reducing sugaracidic compounds glycosides and carbohydrates Alkaloidsshowed the highest presence in abundanceTheweakly acidicfraction analysis isolated from aqueous methanolic extractof leaves of L micranthus showed the presence of terpenoidssteroids acidic compounds flavonoids and carbohydrateLower rate of flavonoids and carbohydrates elicited incomparison with methanolic extract while the amountof terpenoids acidic compounds and steroids remainedunchanged [28] Chemical composition of L micranthus wasfound to be seasonal dependent During April the onset ofrainy season methanolic extract of the leaves harvested fromPAmericana showedhigher concentrations of carbohydratesacidic compounds steroids and alkaloids compared to Julythe time for peak of rainy season Interestingly Tanninssaponins glycosides and reducing sugars were not foundin July samples However higher amounts of flavonoidsand oils were detected in July samples compared to Aprilones [29] Iwalokun and colleagues [30] have investigatedthe phytochemicals such as n-butanol chloroform ethylacetate and water fractions of the methanolic extract of Lmicranthus leaves of Kola nut tree (K acuminata) Moderateand high levels of steroids and terpenoids were detectedin n-butanol fraction while phenolics reducing sugarsand tannins were detected in all fractions together withmoderate level for phenolics and tannins in chloroformfraction Indeed flavonoids and saponins were only presentin ethyl acetate and water fractions respectively Theyhave demonstrated that terpenoids were present in low-to-moderate levels in chloroform and water fractionswhile they were not detected in ethyl acetate fractionPhytochemical studies on L micranthus leaves harvestedfrom six different host trees namely P americana Bnitida K acuminata P macrophylla A indica and Irvingiagabonensis revealed that alkaloids are preponderant in theextracts of K acuminata P Americana and I gabonensisMoreover the phytochemical constituent host dependencywas also shown [31 32] A study on petroleum ether extractof L micranthus leaves parasitic on P americana harvestedat different seasons (January April July and November)showed only presence of alkaloids in April and July andproved harvesting period dependency in phytochemicals ofL micranthus [33] In several studies attempting to identifythe active compounds responsible for various biologicalactivities of L micranthus especially immunomodulatory

activity a variety of compounds (Table 1) were isolated andtheir structures were characterized (Figure 1)

3 Biological Activities

Fractions pure compounds and crude extracts of plants areprecious and crucial resources for effectivemolecules in treat-ment of different diseases and ailments in animal and human[34] L micranthus has been found to possess antidiabeticantimicrobial antihypertensive hypolipidemic antioxidantantidiarrhoeal and immunomodulatory activities A studyby Edem and Usoh [35] demonstrated that the use of Lmicranthus is safe and without adverse biochemical effectsor hepatocellular damages in rats They have administereddifferent doses of the water extract of L micranthus leavesfrom 275 to 827mgkg for 21 days on male albino Wistarrats Blood samples analysis did not reveal any significantchanges in the level of protein urea glucose bilirubincholesterol alkaline phosphatase and aspartate transami-naseHowever significant reductionwas observed in the levelof alanine transaminase enzyme by using 551 and 827mgkgof the extract However an in vitro study on aqueous leafextract of L micranthus indicated cytotoxic genotoxic andmitodepressive effects of that extract againstAllium cepa rootcells especially at dose beyond pharmacological range [36]They showed a significant inhibition of root growth with aneffective concentration (EC

50) of 282mgmL The extract

revealed dose-dependent decrease in mitotic index by 24ndash274 using a range from 5 to 40mgmL of the extract exceptat 25mgmL in which 119 elevation was reported com-pared to 50 decrease for sodium azide used at 100 120583gmLas positive control Hence for safety reasons using the lowerconcentrations of L micranthus for human phytomedicinein prolonged use coupled with in vivo genotoxic tests issuggested [36]

31 Immunomodulatory Activity Stimulation of humanimmune system has been identified as a possible pathwayto inhibit the progression of some diseases without elicitingadverse side effects [37 38] However immune systemstimulation is a desired response if overall process culminateswith cure or faster convalescence from sickness [39 40] Onefolkloric use of L micranthus is due to its ability to enhancethe immune system with concomitant quicker convalescence[10] An in vivo study on aqueous-methanol extract fromL micranthus leaves harvested from five different host treeshas investigated the immunomodulatory activity in rat andmice models including the cyclophosphamide-inducedmyelosuppression (CIM) test the humoral mediatedantibody titration (AT) test total and differential leukocytecount (TLC and DLC) and the cellular mediated delayed-type hypersensitivity reaction (DTHR) test [10] Accordingto the results the extracts (with overall order of activityfrom K acuminate gt Citrus spp gt P Americana gt Parkiabiglobosa gt P macrophylla) were found to be potent andsafe complementary or alternative medicines to cure theimmunodeficiency conditions without any toxicity (LD

50

Evidence-Based Complementary and Alternative Medicine 3

Table1Ph

ytochemistry

andbioactivity

ofcompo

unds

isolatedfro

mLmicranthus

Plantp

art

Com

poun

dCod

eCh

emicalCa

tegory

Biologicalactiv

ityHosttree

Reference

Leafytwigs

Linamarin

gallate

1Ph

enolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Walsurasid

eB2

Phenolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Catechin

3Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[13]

Epicatechin

4Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[14]

Epicatechin3-O-gallate

5Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[15]

Epicatechin3-O-(3-O-m

ethyl)gallate

6Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[16]

Epicatechin3-O-(35-O-dim

ethyl)gallate

7Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[17]

Epicatechin3-O-(345-O-tr

imethyl)gallate

8Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[18]

Quercetin

3-O-120573-D

-glucopyrano

side

9Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[19]

Rutin

10Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[20]

Peltatosid

e11

Polyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[21]

Leaves

-(-)catechin-7-O

-rhamno

side

12Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

-(-)catechin-3-O

-rhamno

side

13Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

41015840-m

etho

xy-catechin-7-O-rhamno

side

14Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-palmitate

15Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-stearate

16Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-eicosanoate

17Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

stigm

ast-7

20(21)-diene-3120573

-hydroxy-6-one

18Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

3120573-hydroxystigmast-2

3-ene(stigmast-2

3-en-3120573-ol)

19Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

Lupeol

20Triterpenoid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[25]

Lupinine

21Alkaloid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

Lorantho

icacid

22Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

4 Evidence-Based Complementary and Alternative Medicine

OO

OO

OH

OH

OH

HO

HOHO

N

1

(a)

OO OH

OH

OHOH

OH

OO

O

HOHO

2

(b)

OHO

OHR

OH

OHOH

OH

3 R =4 R =

(c)

OH

OH

OH

O

O

O

HO

R1

R2

R3

5 R1 = R2 = R3 = OH6 R1 = R2 = OH R3 = OCH3

7 R1 = R3 = OCH3 R2 = OH8 R1 = R2 = R3 = OCH3

(d)

OHOH

OHO

OHOR

O9 R = 120573-D-Glu10R = 120572-L-Rha(1rarr6)-120573-D-Glu11R = 120572-L-Ara(1rarr6)-120573-D-Glu

(e)

OHOH

OO

OHOH

O

OHOHOH

H3C

12

(f)

OHOH

OHO

OH

OHOH OH

OO13 CH3

(g)

OH

OO

OHOH

O

OHOHOH

OCH3

14

H3C

(h)

OHO

OOH

CH3(CH2)n15n = 1216n = 1417n = 16

(i)

OHO

18

(j)

HOH

H

19

(k)

H H

H

HO

CH3

CH3CH3

CH3

CH3

H2C

H3C

20

CH3

(l)

N

OH

21

(m)

O

HOOC

H3CO

H3CO

CH2

22

(n)

Figure 1 Chemical structure of chemical compounds isolated from L micranthus

Evidence-Based Complementary and Alternative Medicine 5

values gt 5000mgkg for acute toxicity tests) Leaves extractparasitic on K acuminate at a dose of 200mgkg caused13969 stimulation of total leukocyte in mice comparedto 7535 increase for levamisole (25mgkg) as a standardimmunostimulatory drug At dose of 100mgkg it alsoshowed 175 stimulation on DTHR in immunocompetentmice compared to 12250 increase for levamisole aspositive control 7135 and 8153 of primary andsecondary stimulation on antibody titration in rats ata dose of 100mgkg of leaves extract also exhibited thesignificant immunomodulatory effect compared to 2450and 040 of primary and secondary stimulation forlevamisole (25mgkg) respectively [10 41] Results fromanother study by the same group showed that ethanoland n-hexane leaves extracts parasitic on P americanaat doses from 100 to 400mgkg also exhibited a dose-dependent immunomodulatory activity assessed by DTHRand CIM models in mice Results showed over 170 ofstimulation for both extracts at 400mgkg dose [42] Theimmunomodulatory analysis of five different extracts ofL micranthus leaves parasitic on K acuminata namelyn-hexane chloroform ethyl acetate acetone and methanolby DTHR test in experimental mice and their phytochemicalevaluation of the fractions demonstrated that themost activefractions were either mainly terpenoidal flavonoidal orsteroidal [43]The results also confirmed the most significantimmunostimulatory effects for chloroform extract with31111 and 12222 enhancement in stimulation using 250and 500mgkg of the extract respectively The compounds12ndash14 at dose of 100 120583gmL showed increasing effects onC57BL6 mice splenocytes proliferation with 9149 9517and 9423 stimulation values respectively comparedto 1609 stimulation for 10 120583gmL of lipopolysaccharide(LPS) as positive control However compounds 12 13and 14 exhibited moderate stimulatory effect on CD69molecule expression [22] The compound 15 with dose of100 120583gmL exhibited a weak immunostimulatory activityby inducing 2444 and 8698 stimulation of micesplenocytes proliferation and early activation of CD69molecule respectively In addition it also showed anonsignificant effect on IL-8 receptor expression [44] Thesteroids compounds of 18 and 19 at a dose of 100 120583gmLexhibited significant immunostimulatory activity on theC57BL6 mice splenocytes with 46 and 43 stimulationrespectively compared to 769 increase for the negativecontrol although CD69 expression assay revealed minimalstimulation The compounds 16 and 17 with the sameconcentration showed weaker stimulations of 30 and29 respectively on the C57BL6 mice splenocytes [24]Also a mild immunostimulatory activity was observed forcompound 20 when it was tested on C57BL6 splenocytes[25] However 6984 and 5634 stimulation elicited fromcompounds 21 and 22 at a dose of 25 120583gmL for proliferationanalysis on mice splenocytes (C57BL6) compared to 758value for unstimulated control The CD69 expression assayalso exhibited significant proliferation values of 271 and231 for compounds of 21 and 22 respectively [27]

32 Antidiabetic Activity Diabetes mellitus is one of theprevalent and serious chronic diseases around the world[45] Therefore finding the promising ways to improve thequality of life for diabetic patients and preventing or reversingdiabetic complications necessitate investigations among thearsenal of herbs [46] Osadebe and colleagues [32] havestudied the anti-diabetic activity of the methanolic extractsof leaves of L micranthus parasitic on P americana Bnitida K acuminata P macrophylla and A indica Theextracts were found to possess significant dose-dependentantihyperglycemic effects in alloxan-induced diabetic albinoand normoglycemic rats respectivelyThemaximum activityof the methanolic extract of L micranthus (400mgkg)harvested from P americana on alloxan-induced diabeticrats showed 8259 reduction of blood sugar level at 24 hafter administration determined by o-toluidine spectropho-tometric method which is statistically comparable with the8334 of reduction for glibenclamide as a positive controlMethanolic extracts of L micranthus from five different hosttrees did not show any toxicity according the acute toxicitytests in mice (LD

50values of 11650 11650 5900 5900 and

5900mgkg for P americana B nitida K acuminata Pmacrophylla andA indica resp)The leaves of L micranthusparasitic on K acuminata A indica and B nitida showedmore significant antihyperglycemic activity among the otherhost trees investigated The results demonstrated that theantidiabetic effect of the extract was found to be dependenton the host plant species The weakly acidic fraction of theaqueous methanol extract of the leaves of L micranthusparasitic on P americana revealed anti-diabetic activity inalloxan-induced diabetic rats The low-acidic fraction at thedose of 400mgkg reduced 6660 of blood sugar level ofalloxan-induced diabetic rats at 24 hours after administration[28] However Osadebe and colleagues [29] have studiedthe seasonal variation for the anti-diabetic effect of theaqueous methanolic extract of the leaves of L micranthusparasitic on P americana in alloxan-induced diabetic ratsThe study demonstrated that anti-diabetic effect of the extractis seasonal and dose dependent with the highest activitybeing at the peak of the rainy season The results revealed392 and 475 fasting blood sugar reduction after 6hours consumption of 400mgkg of April and July samplesrespectively with 83 difference due to effect of seasonalvariation on chemical content of leavesHigher concentrationfor flavonoids in peak of the rainy season compared to theonset of rainy season could be responsible for the observedhigher anti-diabetic activity in July However there is no dataavailable for the particular bioactive compound(s) from Lmicranthuswith knownmechanism for anti-diabetic activityTherefore this is an open area for the future research aroundthis plant Uzochukwu and Osadeb [47] have studied acomparative evaluation of antidiabetic activities of crudemethanolic extract and flavonoids extract of L micranthusharvested from K acuminata in alloxan-induced diabeticrats Results revealed that flavonoids extract (200mgkg)showed significant anti-diabetic effect within one hour ofadministration while the methanolic extract (200mgkg)

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 2: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

2 Evidence-Based Complementary and Alternative Medicine

investigations [1 2 10 11] In Nigeria and South AfricaL micranthus has been widely used as ethnomedicine fortreatment of hypertension diabetes and schizophrenia andas an immune system booster [10]

2 Phytochemistry

Extensive phytochemical evaluations of L micranthusextracts demonstrated the presence of various phyto-constituents and compounds Crude methanolic extractfrom leaves of L micranthus harvested from P americanawasfound to possess terpenoids steroids oils proteins resinsflavonoids tannins saponins alkaloids reducing sugaracidic compounds glycosides and carbohydrates Alkaloidsshowed the highest presence in abundanceTheweakly acidicfraction analysis isolated from aqueous methanolic extractof leaves of L micranthus showed the presence of terpenoidssteroids acidic compounds flavonoids and carbohydrateLower rate of flavonoids and carbohydrates elicited incomparison with methanolic extract while the amountof terpenoids acidic compounds and steroids remainedunchanged [28] Chemical composition of L micranthus wasfound to be seasonal dependent During April the onset ofrainy season methanolic extract of the leaves harvested fromPAmericana showedhigher concentrations of carbohydratesacidic compounds steroids and alkaloids compared to Julythe time for peak of rainy season Interestingly Tanninssaponins glycosides and reducing sugars were not foundin July samples However higher amounts of flavonoidsand oils were detected in July samples compared to Aprilones [29] Iwalokun and colleagues [30] have investigatedthe phytochemicals such as n-butanol chloroform ethylacetate and water fractions of the methanolic extract of Lmicranthus leaves of Kola nut tree (K acuminata) Moderateand high levels of steroids and terpenoids were detectedin n-butanol fraction while phenolics reducing sugarsand tannins were detected in all fractions together withmoderate level for phenolics and tannins in chloroformfraction Indeed flavonoids and saponins were only presentin ethyl acetate and water fractions respectively Theyhave demonstrated that terpenoids were present in low-to-moderate levels in chloroform and water fractionswhile they were not detected in ethyl acetate fractionPhytochemical studies on L micranthus leaves harvestedfrom six different host trees namely P americana Bnitida K acuminata P macrophylla A indica and Irvingiagabonensis revealed that alkaloids are preponderant in theextracts of K acuminata P Americana and I gabonensisMoreover the phytochemical constituent host dependencywas also shown [31 32] A study on petroleum ether extractof L micranthus leaves parasitic on P americana harvestedat different seasons (January April July and November)showed only presence of alkaloids in April and July andproved harvesting period dependency in phytochemicals ofL micranthus [33] In several studies attempting to identifythe active compounds responsible for various biologicalactivities of L micranthus especially immunomodulatory

activity a variety of compounds (Table 1) were isolated andtheir structures were characterized (Figure 1)

3 Biological Activities

Fractions pure compounds and crude extracts of plants areprecious and crucial resources for effectivemolecules in treat-ment of different diseases and ailments in animal and human[34] L micranthus has been found to possess antidiabeticantimicrobial antihypertensive hypolipidemic antioxidantantidiarrhoeal and immunomodulatory activities A studyby Edem and Usoh [35] demonstrated that the use of Lmicranthus is safe and without adverse biochemical effectsor hepatocellular damages in rats They have administereddifferent doses of the water extract of L micranthus leavesfrom 275 to 827mgkg for 21 days on male albino Wistarrats Blood samples analysis did not reveal any significantchanges in the level of protein urea glucose bilirubincholesterol alkaline phosphatase and aspartate transami-naseHowever significant reductionwas observed in the levelof alanine transaminase enzyme by using 551 and 827mgkgof the extract However an in vitro study on aqueous leafextract of L micranthus indicated cytotoxic genotoxic andmitodepressive effects of that extract againstAllium cepa rootcells especially at dose beyond pharmacological range [36]They showed a significant inhibition of root growth with aneffective concentration (EC

50) of 282mgmL The extract

revealed dose-dependent decrease in mitotic index by 24ndash274 using a range from 5 to 40mgmL of the extract exceptat 25mgmL in which 119 elevation was reported com-pared to 50 decrease for sodium azide used at 100 120583gmLas positive control Hence for safety reasons using the lowerconcentrations of L micranthus for human phytomedicinein prolonged use coupled with in vivo genotoxic tests issuggested [36]

31 Immunomodulatory Activity Stimulation of humanimmune system has been identified as a possible pathwayto inhibit the progression of some diseases without elicitingadverse side effects [37 38] However immune systemstimulation is a desired response if overall process culminateswith cure or faster convalescence from sickness [39 40] Onefolkloric use of L micranthus is due to its ability to enhancethe immune system with concomitant quicker convalescence[10] An in vivo study on aqueous-methanol extract fromL micranthus leaves harvested from five different host treeshas investigated the immunomodulatory activity in rat andmice models including the cyclophosphamide-inducedmyelosuppression (CIM) test the humoral mediatedantibody titration (AT) test total and differential leukocytecount (TLC and DLC) and the cellular mediated delayed-type hypersensitivity reaction (DTHR) test [10] Accordingto the results the extracts (with overall order of activityfrom K acuminate gt Citrus spp gt P Americana gt Parkiabiglobosa gt P macrophylla) were found to be potent andsafe complementary or alternative medicines to cure theimmunodeficiency conditions without any toxicity (LD

50

Evidence-Based Complementary and Alternative Medicine 3

Table1Ph

ytochemistry

andbioactivity

ofcompo

unds

isolatedfro

mLmicranthus

Plantp

art

Com

poun

dCod

eCh

emicalCa

tegory

Biologicalactiv

ityHosttree

Reference

Leafytwigs

Linamarin

gallate

1Ph

enolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Walsurasid

eB2

Phenolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Catechin

3Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[13]

Epicatechin

4Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[14]

Epicatechin3-O-gallate

5Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[15]

Epicatechin3-O-(3-O-m

ethyl)gallate

6Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[16]

Epicatechin3-O-(35-O-dim

ethyl)gallate

7Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[17]

Epicatechin3-O-(345-O-tr

imethyl)gallate

8Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[18]

Quercetin

3-O-120573-D

-glucopyrano

side

9Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[19]

Rutin

10Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[20]

Peltatosid

e11

Polyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[21]

Leaves

-(-)catechin-7-O

-rhamno

side

12Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

-(-)catechin-3-O

-rhamno

side

13Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

41015840-m

etho

xy-catechin-7-O-rhamno

side

14Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-palmitate

15Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-stearate

16Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-eicosanoate

17Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

stigm

ast-7

20(21)-diene-3120573

-hydroxy-6-one

18Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

3120573-hydroxystigmast-2

3-ene(stigmast-2

3-en-3120573-ol)

19Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

Lupeol

20Triterpenoid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[25]

Lupinine

21Alkaloid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

Lorantho

icacid

22Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

4 Evidence-Based Complementary and Alternative Medicine

OO

OO

OH

OH

OH

HO

HOHO

N

1

(a)

OO OH

OH

OHOH

OH

OO

O

HOHO

2

(b)

OHO

OHR

OH

OHOH

OH

3 R =4 R =

(c)

OH

OH

OH

O

O

O

HO

R1

R2

R3

5 R1 = R2 = R3 = OH6 R1 = R2 = OH R3 = OCH3

7 R1 = R3 = OCH3 R2 = OH8 R1 = R2 = R3 = OCH3

(d)

OHOH

OHO

OHOR

O9 R = 120573-D-Glu10R = 120572-L-Rha(1rarr6)-120573-D-Glu11R = 120572-L-Ara(1rarr6)-120573-D-Glu

(e)

OHOH

OO

OHOH

O

OHOHOH

H3C

12

(f)

OHOH

OHO

OH

OHOH OH

OO13 CH3

(g)

OH

OO

OHOH

O

OHOHOH

OCH3

14

H3C

(h)

OHO

OOH

CH3(CH2)n15n = 1216n = 1417n = 16

(i)

OHO

18

(j)

HOH

H

19

(k)

H H

H

HO

CH3

CH3CH3

CH3

CH3

H2C

H3C

20

CH3

(l)

N

OH

21

(m)

O

HOOC

H3CO

H3CO

CH2

22

(n)

Figure 1 Chemical structure of chemical compounds isolated from L micranthus

Evidence-Based Complementary and Alternative Medicine 5

values gt 5000mgkg for acute toxicity tests) Leaves extractparasitic on K acuminate at a dose of 200mgkg caused13969 stimulation of total leukocyte in mice comparedto 7535 increase for levamisole (25mgkg) as a standardimmunostimulatory drug At dose of 100mgkg it alsoshowed 175 stimulation on DTHR in immunocompetentmice compared to 12250 increase for levamisole aspositive control 7135 and 8153 of primary andsecondary stimulation on antibody titration in rats ata dose of 100mgkg of leaves extract also exhibited thesignificant immunomodulatory effect compared to 2450and 040 of primary and secondary stimulation forlevamisole (25mgkg) respectively [10 41] Results fromanother study by the same group showed that ethanoland n-hexane leaves extracts parasitic on P americanaat doses from 100 to 400mgkg also exhibited a dose-dependent immunomodulatory activity assessed by DTHRand CIM models in mice Results showed over 170 ofstimulation for both extracts at 400mgkg dose [42] Theimmunomodulatory analysis of five different extracts ofL micranthus leaves parasitic on K acuminata namelyn-hexane chloroform ethyl acetate acetone and methanolby DTHR test in experimental mice and their phytochemicalevaluation of the fractions demonstrated that themost activefractions were either mainly terpenoidal flavonoidal orsteroidal [43]The results also confirmed the most significantimmunostimulatory effects for chloroform extract with31111 and 12222 enhancement in stimulation using 250and 500mgkg of the extract respectively The compounds12ndash14 at dose of 100 120583gmL showed increasing effects onC57BL6 mice splenocytes proliferation with 9149 9517and 9423 stimulation values respectively comparedto 1609 stimulation for 10 120583gmL of lipopolysaccharide(LPS) as positive control However compounds 12 13and 14 exhibited moderate stimulatory effect on CD69molecule expression [22] The compound 15 with dose of100 120583gmL exhibited a weak immunostimulatory activityby inducing 2444 and 8698 stimulation of micesplenocytes proliferation and early activation of CD69molecule respectively In addition it also showed anonsignificant effect on IL-8 receptor expression [44] Thesteroids compounds of 18 and 19 at a dose of 100 120583gmLexhibited significant immunostimulatory activity on theC57BL6 mice splenocytes with 46 and 43 stimulationrespectively compared to 769 increase for the negativecontrol although CD69 expression assay revealed minimalstimulation The compounds 16 and 17 with the sameconcentration showed weaker stimulations of 30 and29 respectively on the C57BL6 mice splenocytes [24]Also a mild immunostimulatory activity was observed forcompound 20 when it was tested on C57BL6 splenocytes[25] However 6984 and 5634 stimulation elicited fromcompounds 21 and 22 at a dose of 25 120583gmL for proliferationanalysis on mice splenocytes (C57BL6) compared to 758value for unstimulated control The CD69 expression assayalso exhibited significant proliferation values of 271 and231 for compounds of 21 and 22 respectively [27]

32 Antidiabetic Activity Diabetes mellitus is one of theprevalent and serious chronic diseases around the world[45] Therefore finding the promising ways to improve thequality of life for diabetic patients and preventing or reversingdiabetic complications necessitate investigations among thearsenal of herbs [46] Osadebe and colleagues [32] havestudied the anti-diabetic activity of the methanolic extractsof leaves of L micranthus parasitic on P americana Bnitida K acuminata P macrophylla and A indica Theextracts were found to possess significant dose-dependentantihyperglycemic effects in alloxan-induced diabetic albinoand normoglycemic rats respectivelyThemaximum activityof the methanolic extract of L micranthus (400mgkg)harvested from P americana on alloxan-induced diabeticrats showed 8259 reduction of blood sugar level at 24 hafter administration determined by o-toluidine spectropho-tometric method which is statistically comparable with the8334 of reduction for glibenclamide as a positive controlMethanolic extracts of L micranthus from five different hosttrees did not show any toxicity according the acute toxicitytests in mice (LD

50values of 11650 11650 5900 5900 and

5900mgkg for P americana B nitida K acuminata Pmacrophylla andA indica resp)The leaves of L micranthusparasitic on K acuminata A indica and B nitida showedmore significant antihyperglycemic activity among the otherhost trees investigated The results demonstrated that theantidiabetic effect of the extract was found to be dependenton the host plant species The weakly acidic fraction of theaqueous methanol extract of the leaves of L micranthusparasitic on P americana revealed anti-diabetic activity inalloxan-induced diabetic rats The low-acidic fraction at thedose of 400mgkg reduced 6660 of blood sugar level ofalloxan-induced diabetic rats at 24 hours after administration[28] However Osadebe and colleagues [29] have studiedthe seasonal variation for the anti-diabetic effect of theaqueous methanolic extract of the leaves of L micranthusparasitic on P americana in alloxan-induced diabetic ratsThe study demonstrated that anti-diabetic effect of the extractis seasonal and dose dependent with the highest activitybeing at the peak of the rainy season The results revealed392 and 475 fasting blood sugar reduction after 6hours consumption of 400mgkg of April and July samplesrespectively with 83 difference due to effect of seasonalvariation on chemical content of leavesHigher concentrationfor flavonoids in peak of the rainy season compared to theonset of rainy season could be responsible for the observedhigher anti-diabetic activity in July However there is no dataavailable for the particular bioactive compound(s) from Lmicranthuswith knownmechanism for anti-diabetic activityTherefore this is an open area for the future research aroundthis plant Uzochukwu and Osadeb [47] have studied acomparative evaluation of antidiabetic activities of crudemethanolic extract and flavonoids extract of L micranthusharvested from K acuminata in alloxan-induced diabeticrats Results revealed that flavonoids extract (200mgkg)showed significant anti-diabetic effect within one hour ofadministration while the methanolic extract (200mgkg)

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 3: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Evidence-Based Complementary and Alternative Medicine 3

Table1Ph

ytochemistry

andbioactivity

ofcompo

unds

isolatedfro

mLmicranthus

Plantp

art

Com

poun

dCod

eCh

emicalCa

tegory

Biologicalactiv

ityHosttree

Reference

Leafytwigs

Linamarin

gallate

1Ph

enolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Walsurasid

eB2

Phenolicsg

lycosid

eAntioxidant

activ

ityHevea

brasiliensis

[12]

Catechin

3Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[13]

Epicatechin

4Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[14]

Epicatechin3-O-gallate

5Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[15]

Epicatechin3-O-(3-O-m

ethyl)gallate

6Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[16]

Epicatechin3-O-(35-O-dim

ethyl)gallate

7Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[17]

Epicatechin3-O-(345-O-tr

imethyl)gallate

8Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[18]

Quercetin

3-O-120573-D

-glucopyrano

side

9Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[19]

Rutin

10Po

lyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[20]

Peltatosid

e11

Polyph

enol

Antioxidant

activ

ityHevea

brasiliensis

[21]

Leaves

-(-)catechin-7-O

-rhamno

side

12Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

-(-)catechin-3-O

-rhamno

side

13Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

41015840-m

etho

xy-catechin-7-O-rhamno

side

14Po

lyph

enol

Immun

omod

ulatoryandantio

xidant

activ

ityKo

laacum

inata

[22]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-palmitate

15Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-stearate

16Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

712057315120572

-dihydroxy-lu

p-20(29)-en-3120573

-O-eicosanoate

17Triterpenoidester

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[23]

stigm

ast-7

20(21)-diene-3120573

-hydroxy-6-one

18Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

3120573-hydroxystigmast-2

3-ene(stigmast-2

3-en-3120573-ol)

19Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[24]

Lupeol

20Triterpenoid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[25]

Lupinine

21Alkaloid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

Lorantho

icacid

22Steroid

Immun

omod

ulatoryactiv

ityKo

laacum

inata

[2627]

4 Evidence-Based Complementary and Alternative Medicine

OO

OO

OH

OH

OH

HO

HOHO

N

1

(a)

OO OH

OH

OHOH

OH

OO

O

HOHO

2

(b)

OHO

OHR

OH

OHOH

OH

3 R =4 R =

(c)

OH

OH

OH

O

O

O

HO

R1

R2

R3

5 R1 = R2 = R3 = OH6 R1 = R2 = OH R3 = OCH3

7 R1 = R3 = OCH3 R2 = OH8 R1 = R2 = R3 = OCH3

(d)

OHOH

OHO

OHOR

O9 R = 120573-D-Glu10R = 120572-L-Rha(1rarr6)-120573-D-Glu11R = 120572-L-Ara(1rarr6)-120573-D-Glu

(e)

OHOH

OO

OHOH

O

OHOHOH

H3C

12

(f)

OHOH

OHO

OH

OHOH OH

OO13 CH3

(g)

OH

OO

OHOH

O

OHOHOH

OCH3

14

H3C

(h)

OHO

OOH

CH3(CH2)n15n = 1216n = 1417n = 16

(i)

OHO

18

(j)

HOH

H

19

(k)

H H

H

HO

CH3

CH3CH3

CH3

CH3

H2C

H3C

20

CH3

(l)

N

OH

21

(m)

O

HOOC

H3CO

H3CO

CH2

22

(n)

Figure 1 Chemical structure of chemical compounds isolated from L micranthus

Evidence-Based Complementary and Alternative Medicine 5

values gt 5000mgkg for acute toxicity tests) Leaves extractparasitic on K acuminate at a dose of 200mgkg caused13969 stimulation of total leukocyte in mice comparedto 7535 increase for levamisole (25mgkg) as a standardimmunostimulatory drug At dose of 100mgkg it alsoshowed 175 stimulation on DTHR in immunocompetentmice compared to 12250 increase for levamisole aspositive control 7135 and 8153 of primary andsecondary stimulation on antibody titration in rats ata dose of 100mgkg of leaves extract also exhibited thesignificant immunomodulatory effect compared to 2450and 040 of primary and secondary stimulation forlevamisole (25mgkg) respectively [10 41] Results fromanother study by the same group showed that ethanoland n-hexane leaves extracts parasitic on P americanaat doses from 100 to 400mgkg also exhibited a dose-dependent immunomodulatory activity assessed by DTHRand CIM models in mice Results showed over 170 ofstimulation for both extracts at 400mgkg dose [42] Theimmunomodulatory analysis of five different extracts ofL micranthus leaves parasitic on K acuminata namelyn-hexane chloroform ethyl acetate acetone and methanolby DTHR test in experimental mice and their phytochemicalevaluation of the fractions demonstrated that themost activefractions were either mainly terpenoidal flavonoidal orsteroidal [43]The results also confirmed the most significantimmunostimulatory effects for chloroform extract with31111 and 12222 enhancement in stimulation using 250and 500mgkg of the extract respectively The compounds12ndash14 at dose of 100 120583gmL showed increasing effects onC57BL6 mice splenocytes proliferation with 9149 9517and 9423 stimulation values respectively comparedto 1609 stimulation for 10 120583gmL of lipopolysaccharide(LPS) as positive control However compounds 12 13and 14 exhibited moderate stimulatory effect on CD69molecule expression [22] The compound 15 with dose of100 120583gmL exhibited a weak immunostimulatory activityby inducing 2444 and 8698 stimulation of micesplenocytes proliferation and early activation of CD69molecule respectively In addition it also showed anonsignificant effect on IL-8 receptor expression [44] Thesteroids compounds of 18 and 19 at a dose of 100 120583gmLexhibited significant immunostimulatory activity on theC57BL6 mice splenocytes with 46 and 43 stimulationrespectively compared to 769 increase for the negativecontrol although CD69 expression assay revealed minimalstimulation The compounds 16 and 17 with the sameconcentration showed weaker stimulations of 30 and29 respectively on the C57BL6 mice splenocytes [24]Also a mild immunostimulatory activity was observed forcompound 20 when it was tested on C57BL6 splenocytes[25] However 6984 and 5634 stimulation elicited fromcompounds 21 and 22 at a dose of 25 120583gmL for proliferationanalysis on mice splenocytes (C57BL6) compared to 758value for unstimulated control The CD69 expression assayalso exhibited significant proliferation values of 271 and231 for compounds of 21 and 22 respectively [27]

32 Antidiabetic Activity Diabetes mellitus is one of theprevalent and serious chronic diseases around the world[45] Therefore finding the promising ways to improve thequality of life for diabetic patients and preventing or reversingdiabetic complications necessitate investigations among thearsenal of herbs [46] Osadebe and colleagues [32] havestudied the anti-diabetic activity of the methanolic extractsof leaves of L micranthus parasitic on P americana Bnitida K acuminata P macrophylla and A indica Theextracts were found to possess significant dose-dependentantihyperglycemic effects in alloxan-induced diabetic albinoand normoglycemic rats respectivelyThemaximum activityof the methanolic extract of L micranthus (400mgkg)harvested from P americana on alloxan-induced diabeticrats showed 8259 reduction of blood sugar level at 24 hafter administration determined by o-toluidine spectropho-tometric method which is statistically comparable with the8334 of reduction for glibenclamide as a positive controlMethanolic extracts of L micranthus from five different hosttrees did not show any toxicity according the acute toxicitytests in mice (LD

50values of 11650 11650 5900 5900 and

5900mgkg for P americana B nitida K acuminata Pmacrophylla andA indica resp)The leaves of L micranthusparasitic on K acuminata A indica and B nitida showedmore significant antihyperglycemic activity among the otherhost trees investigated The results demonstrated that theantidiabetic effect of the extract was found to be dependenton the host plant species The weakly acidic fraction of theaqueous methanol extract of the leaves of L micranthusparasitic on P americana revealed anti-diabetic activity inalloxan-induced diabetic rats The low-acidic fraction at thedose of 400mgkg reduced 6660 of blood sugar level ofalloxan-induced diabetic rats at 24 hours after administration[28] However Osadebe and colleagues [29] have studiedthe seasonal variation for the anti-diabetic effect of theaqueous methanolic extract of the leaves of L micranthusparasitic on P americana in alloxan-induced diabetic ratsThe study demonstrated that anti-diabetic effect of the extractis seasonal and dose dependent with the highest activitybeing at the peak of the rainy season The results revealed392 and 475 fasting blood sugar reduction after 6hours consumption of 400mgkg of April and July samplesrespectively with 83 difference due to effect of seasonalvariation on chemical content of leavesHigher concentrationfor flavonoids in peak of the rainy season compared to theonset of rainy season could be responsible for the observedhigher anti-diabetic activity in July However there is no dataavailable for the particular bioactive compound(s) from Lmicranthuswith knownmechanism for anti-diabetic activityTherefore this is an open area for the future research aroundthis plant Uzochukwu and Osadeb [47] have studied acomparative evaluation of antidiabetic activities of crudemethanolic extract and flavonoids extract of L micranthusharvested from K acuminata in alloxan-induced diabeticrats Results revealed that flavonoids extract (200mgkg)showed significant anti-diabetic effect within one hour ofadministration while the methanolic extract (200mgkg)

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 4: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

4 Evidence-Based Complementary and Alternative Medicine

OO

OO

OH

OH

OH

HO

HOHO

N

1

(a)

OO OH

OH

OHOH

OH

OO

O

HOHO

2

(b)

OHO

OHR

OH

OHOH

OH

3 R =4 R =

(c)

OH

OH

OH

O

O

O

HO

R1

R2

R3

5 R1 = R2 = R3 = OH6 R1 = R2 = OH R3 = OCH3

7 R1 = R3 = OCH3 R2 = OH8 R1 = R2 = R3 = OCH3

(d)

OHOH

OHO

OHOR

O9 R = 120573-D-Glu10R = 120572-L-Rha(1rarr6)-120573-D-Glu11R = 120572-L-Ara(1rarr6)-120573-D-Glu

(e)

OHOH

OO

OHOH

O

OHOHOH

H3C

12

(f)

OHOH

OHO

OH

OHOH OH

OO13 CH3

(g)

OH

OO

OHOH

O

OHOHOH

OCH3

14

H3C

(h)

OHO

OOH

CH3(CH2)n15n = 1216n = 1417n = 16

(i)

OHO

18

(j)

HOH

H

19

(k)

H H

H

HO

CH3

CH3CH3

CH3

CH3

H2C

H3C

20

CH3

(l)

N

OH

21

(m)

O

HOOC

H3CO

H3CO

CH2

22

(n)

Figure 1 Chemical structure of chemical compounds isolated from L micranthus

Evidence-Based Complementary and Alternative Medicine 5

values gt 5000mgkg for acute toxicity tests) Leaves extractparasitic on K acuminate at a dose of 200mgkg caused13969 stimulation of total leukocyte in mice comparedto 7535 increase for levamisole (25mgkg) as a standardimmunostimulatory drug At dose of 100mgkg it alsoshowed 175 stimulation on DTHR in immunocompetentmice compared to 12250 increase for levamisole aspositive control 7135 and 8153 of primary andsecondary stimulation on antibody titration in rats ata dose of 100mgkg of leaves extract also exhibited thesignificant immunomodulatory effect compared to 2450and 040 of primary and secondary stimulation forlevamisole (25mgkg) respectively [10 41] Results fromanother study by the same group showed that ethanoland n-hexane leaves extracts parasitic on P americanaat doses from 100 to 400mgkg also exhibited a dose-dependent immunomodulatory activity assessed by DTHRand CIM models in mice Results showed over 170 ofstimulation for both extracts at 400mgkg dose [42] Theimmunomodulatory analysis of five different extracts ofL micranthus leaves parasitic on K acuminata namelyn-hexane chloroform ethyl acetate acetone and methanolby DTHR test in experimental mice and their phytochemicalevaluation of the fractions demonstrated that themost activefractions were either mainly terpenoidal flavonoidal orsteroidal [43]The results also confirmed the most significantimmunostimulatory effects for chloroform extract with31111 and 12222 enhancement in stimulation using 250and 500mgkg of the extract respectively The compounds12ndash14 at dose of 100 120583gmL showed increasing effects onC57BL6 mice splenocytes proliferation with 9149 9517and 9423 stimulation values respectively comparedto 1609 stimulation for 10 120583gmL of lipopolysaccharide(LPS) as positive control However compounds 12 13and 14 exhibited moderate stimulatory effect on CD69molecule expression [22] The compound 15 with dose of100 120583gmL exhibited a weak immunostimulatory activityby inducing 2444 and 8698 stimulation of micesplenocytes proliferation and early activation of CD69molecule respectively In addition it also showed anonsignificant effect on IL-8 receptor expression [44] Thesteroids compounds of 18 and 19 at a dose of 100 120583gmLexhibited significant immunostimulatory activity on theC57BL6 mice splenocytes with 46 and 43 stimulationrespectively compared to 769 increase for the negativecontrol although CD69 expression assay revealed minimalstimulation The compounds 16 and 17 with the sameconcentration showed weaker stimulations of 30 and29 respectively on the C57BL6 mice splenocytes [24]Also a mild immunostimulatory activity was observed forcompound 20 when it was tested on C57BL6 splenocytes[25] However 6984 and 5634 stimulation elicited fromcompounds 21 and 22 at a dose of 25 120583gmL for proliferationanalysis on mice splenocytes (C57BL6) compared to 758value for unstimulated control The CD69 expression assayalso exhibited significant proliferation values of 271 and231 for compounds of 21 and 22 respectively [27]

32 Antidiabetic Activity Diabetes mellitus is one of theprevalent and serious chronic diseases around the world[45] Therefore finding the promising ways to improve thequality of life for diabetic patients and preventing or reversingdiabetic complications necessitate investigations among thearsenal of herbs [46] Osadebe and colleagues [32] havestudied the anti-diabetic activity of the methanolic extractsof leaves of L micranthus parasitic on P americana Bnitida K acuminata P macrophylla and A indica Theextracts were found to possess significant dose-dependentantihyperglycemic effects in alloxan-induced diabetic albinoand normoglycemic rats respectivelyThemaximum activityof the methanolic extract of L micranthus (400mgkg)harvested from P americana on alloxan-induced diabeticrats showed 8259 reduction of blood sugar level at 24 hafter administration determined by o-toluidine spectropho-tometric method which is statistically comparable with the8334 of reduction for glibenclamide as a positive controlMethanolic extracts of L micranthus from five different hosttrees did not show any toxicity according the acute toxicitytests in mice (LD

50values of 11650 11650 5900 5900 and

5900mgkg for P americana B nitida K acuminata Pmacrophylla andA indica resp)The leaves of L micranthusparasitic on K acuminata A indica and B nitida showedmore significant antihyperglycemic activity among the otherhost trees investigated The results demonstrated that theantidiabetic effect of the extract was found to be dependenton the host plant species The weakly acidic fraction of theaqueous methanol extract of the leaves of L micranthusparasitic on P americana revealed anti-diabetic activity inalloxan-induced diabetic rats The low-acidic fraction at thedose of 400mgkg reduced 6660 of blood sugar level ofalloxan-induced diabetic rats at 24 hours after administration[28] However Osadebe and colleagues [29] have studiedthe seasonal variation for the anti-diabetic effect of theaqueous methanolic extract of the leaves of L micranthusparasitic on P americana in alloxan-induced diabetic ratsThe study demonstrated that anti-diabetic effect of the extractis seasonal and dose dependent with the highest activitybeing at the peak of the rainy season The results revealed392 and 475 fasting blood sugar reduction after 6hours consumption of 400mgkg of April and July samplesrespectively with 83 difference due to effect of seasonalvariation on chemical content of leavesHigher concentrationfor flavonoids in peak of the rainy season compared to theonset of rainy season could be responsible for the observedhigher anti-diabetic activity in July However there is no dataavailable for the particular bioactive compound(s) from Lmicranthuswith knownmechanism for anti-diabetic activityTherefore this is an open area for the future research aroundthis plant Uzochukwu and Osadeb [47] have studied acomparative evaluation of antidiabetic activities of crudemethanolic extract and flavonoids extract of L micranthusharvested from K acuminata in alloxan-induced diabeticrats Results revealed that flavonoids extract (200mgkg)showed significant anti-diabetic effect within one hour ofadministration while the methanolic extract (200mgkg)

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 5: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Evidence-Based Complementary and Alternative Medicine 5

values gt 5000mgkg for acute toxicity tests) Leaves extractparasitic on K acuminate at a dose of 200mgkg caused13969 stimulation of total leukocyte in mice comparedto 7535 increase for levamisole (25mgkg) as a standardimmunostimulatory drug At dose of 100mgkg it alsoshowed 175 stimulation on DTHR in immunocompetentmice compared to 12250 increase for levamisole aspositive control 7135 and 8153 of primary andsecondary stimulation on antibody titration in rats ata dose of 100mgkg of leaves extract also exhibited thesignificant immunomodulatory effect compared to 2450and 040 of primary and secondary stimulation forlevamisole (25mgkg) respectively [10 41] Results fromanother study by the same group showed that ethanoland n-hexane leaves extracts parasitic on P americanaat doses from 100 to 400mgkg also exhibited a dose-dependent immunomodulatory activity assessed by DTHRand CIM models in mice Results showed over 170 ofstimulation for both extracts at 400mgkg dose [42] Theimmunomodulatory analysis of five different extracts ofL micranthus leaves parasitic on K acuminata namelyn-hexane chloroform ethyl acetate acetone and methanolby DTHR test in experimental mice and their phytochemicalevaluation of the fractions demonstrated that themost activefractions were either mainly terpenoidal flavonoidal orsteroidal [43]The results also confirmed the most significantimmunostimulatory effects for chloroform extract with31111 and 12222 enhancement in stimulation using 250and 500mgkg of the extract respectively The compounds12ndash14 at dose of 100 120583gmL showed increasing effects onC57BL6 mice splenocytes proliferation with 9149 9517and 9423 stimulation values respectively comparedto 1609 stimulation for 10 120583gmL of lipopolysaccharide(LPS) as positive control However compounds 12 13and 14 exhibited moderate stimulatory effect on CD69molecule expression [22] The compound 15 with dose of100 120583gmL exhibited a weak immunostimulatory activityby inducing 2444 and 8698 stimulation of micesplenocytes proliferation and early activation of CD69molecule respectively In addition it also showed anonsignificant effect on IL-8 receptor expression [44] Thesteroids compounds of 18 and 19 at a dose of 100 120583gmLexhibited significant immunostimulatory activity on theC57BL6 mice splenocytes with 46 and 43 stimulationrespectively compared to 769 increase for the negativecontrol although CD69 expression assay revealed minimalstimulation The compounds 16 and 17 with the sameconcentration showed weaker stimulations of 30 and29 respectively on the C57BL6 mice splenocytes [24]Also a mild immunostimulatory activity was observed forcompound 20 when it was tested on C57BL6 splenocytes[25] However 6984 and 5634 stimulation elicited fromcompounds 21 and 22 at a dose of 25 120583gmL for proliferationanalysis on mice splenocytes (C57BL6) compared to 758value for unstimulated control The CD69 expression assayalso exhibited significant proliferation values of 271 and231 for compounds of 21 and 22 respectively [27]

32 Antidiabetic Activity Diabetes mellitus is one of theprevalent and serious chronic diseases around the world[45] Therefore finding the promising ways to improve thequality of life for diabetic patients and preventing or reversingdiabetic complications necessitate investigations among thearsenal of herbs [46] Osadebe and colleagues [32] havestudied the anti-diabetic activity of the methanolic extractsof leaves of L micranthus parasitic on P americana Bnitida K acuminata P macrophylla and A indica Theextracts were found to possess significant dose-dependentantihyperglycemic effects in alloxan-induced diabetic albinoand normoglycemic rats respectivelyThemaximum activityof the methanolic extract of L micranthus (400mgkg)harvested from P americana on alloxan-induced diabeticrats showed 8259 reduction of blood sugar level at 24 hafter administration determined by o-toluidine spectropho-tometric method which is statistically comparable with the8334 of reduction for glibenclamide as a positive controlMethanolic extracts of L micranthus from five different hosttrees did not show any toxicity according the acute toxicitytests in mice (LD

50values of 11650 11650 5900 5900 and

5900mgkg for P americana B nitida K acuminata Pmacrophylla andA indica resp)The leaves of L micranthusparasitic on K acuminata A indica and B nitida showedmore significant antihyperglycemic activity among the otherhost trees investigated The results demonstrated that theantidiabetic effect of the extract was found to be dependenton the host plant species The weakly acidic fraction of theaqueous methanol extract of the leaves of L micranthusparasitic on P americana revealed anti-diabetic activity inalloxan-induced diabetic rats The low-acidic fraction at thedose of 400mgkg reduced 6660 of blood sugar level ofalloxan-induced diabetic rats at 24 hours after administration[28] However Osadebe and colleagues [29] have studiedthe seasonal variation for the anti-diabetic effect of theaqueous methanolic extract of the leaves of L micranthusparasitic on P americana in alloxan-induced diabetic ratsThe study demonstrated that anti-diabetic effect of the extractis seasonal and dose dependent with the highest activitybeing at the peak of the rainy season The results revealed392 and 475 fasting blood sugar reduction after 6hours consumption of 400mgkg of April and July samplesrespectively with 83 difference due to effect of seasonalvariation on chemical content of leavesHigher concentrationfor flavonoids in peak of the rainy season compared to theonset of rainy season could be responsible for the observedhigher anti-diabetic activity in July However there is no dataavailable for the particular bioactive compound(s) from Lmicranthuswith knownmechanism for anti-diabetic activityTherefore this is an open area for the future research aroundthis plant Uzochukwu and Osadeb [47] have studied acomparative evaluation of antidiabetic activities of crudemethanolic extract and flavonoids extract of L micranthusharvested from K acuminata in alloxan-induced diabeticrats Results revealed that flavonoids extract (200mgkg)showed significant anti-diabetic effect within one hour ofadministration while the methanolic extract (200mgkg)

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 6: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

6 Evidence-Based Complementary and Alternative Medicine

showed the significant antidiabetic effect within three hoursof administration In addition phytoconstituents of othermembers of Loranthaceae plants possessing antihypertensiveactivity are interestingly similar to L micranthus [48ndash50]

33 Antimicrobial Activity Usingmedicinal plants as antimi-crobial remedy has a long history in both developed anddeveloping countries In addition in contemporarymedicinebecause of unreasonable and indiscriminate consumptionof antimicrobial drugs the infectious microorganisms havedeveloped resistance Therefore controlling the existinginfectious diseases necessitates new alternative antimicrobialdrug regimens [51] Osodebe and Ukwueze have presentedthewide range of data regarding the antimicrobial activities ofL micranthus [31] A study on different extracts of L micran-thus leaves harvested from K acuminata such as methanolicethanolic chloroform and petroleum ether extracts demon-strated the antibacterial activities for all tested extracts againstBacillus subtilis Escherichia coli and Klebsiella pneumoniawhile only petroleum ether extract exerted antifungal activityagainst Aspergillus niger and Candida albicans with the MICof 430 and 173mgmL respectively and no activity againstKlebsiella pneumonia The methanolic extract exhibited themost potent antibacterial effect against Bacillus subtilis andEscherichia coli with MIC of 158 and 148mgmL respec-tively compared to the other tested extracts [52] The ethylacetate fraction of crude petroleum ether extract of Lmicranthus leaves parasitic on K acuminata also showedinhibitory activities against Candida albicans and Bacillussubtilis [53] A comparative investigation on antimicrobialactivities of L micranthus leaves and its phytochemicals fromsix different host trees including P americana B nitidaK acuminata P macrophylla A indica and I gabonensisindicated the relative significant antibacterial activities forL micranthus parasitic on K acuminata and P americanaAlkaloids in these three species were found to be mostabundant Preponderance of alkaloids in these species couldbe responsible for the marked antimicrobial activities Theleaves extract parasitic on P Americana exerted more potentantibacterial activity against Pseudomonas aeruginosa com-pared to amoxicillin while the extracts from A indica Pmacrophylla and I gabonensis exhibited stronger antibacte-rial activity against Staphylococcus aureus in comparisonwithamoxicillin [31] Effect of different harvesting seasons (Jan-uary April July and November) on antimicrobial activity ofpetroleum ether extracts from L micranthus leaves parasiticon P americana and its phytochemicals also demonstratedseasonal dependency Alkaloids as one of the major groupsof antibacterial candidates was only found in July and AprilAntibacterial activity against Salmonella typhi and Bacillussubtilis was markedly lower in January samples comparedto the extracts from the other monthsrsquo samples [33 54] Inaddition no significant antifungal activity for methanolicextracts of L micranthus leaves harvested fromK acuminataP Americana and I gabonensis was demonstrated against Aniger (MIC gt 3mgmL) and C albicans (MIC gt 4mgmL)compared to ketoconazole (MIC lt 1mgmL) as an approvedantifungal agent [55] To sum up it has been proven that

leaf extracts of L micranthus elicited significant antibacterialactivity against B subtilis P aeruginosa E coli and Staphaureus without significant antifungal activity [56]

34 Antihypertensive Activity Deaths because of hyperten-sion arise out of cardiovascular and cerebrovascular compli-cations including cardiac arrest stroke myocardial infarc-tion congestive heart failure and end-stage renal disease[57] Early detection and commencement of treatment arevital for prevention and delaying the aftermaths and enhancethe chance of longer life for afflicted patients [58] In thelast few decades plants have still remained as a rich sourcefor efficacious safe and cost-effective antihypertensive drugs[59] L micranthus is one of the plants identified with antihy-pertensive activity for humans and animals in sub-SaharanAfrica [60] Aqueous extract of L micranthus (132 gkgper day) exhibited hypotensive effect on normotensive andspontaneous hypertensive rats [61] A noteworthy reductionin the mean arterial pressure (MAP) was obtained in bothgroups of rats without effect on the urinary flow rate orthe respiratory rate In addition the level of total choles-terol exhibited significant reduction on days 6 7 and 8[61] Indeed methanolic extract of leaves of L micranthusdemonstrated a dose-dependent inhibition of blood pressureincrease in adrenaline-induced hypertensive rat Iwalokunand colleagues [30] studied the activity of n-butanol chlo-roform ethyl acetate and water fraction of the methanolicextract of L micranthus leaf harvested from K acuminataon pressor-induced contraction of rat aorta smooth mus-cles N-Butanol fraction showed the highest dose-dependentinhibitory activity (EC

50= 065mgmL and smooth muscle

relaxation of 752) on rat aorta precontracted with nore-pinephrine and KCl followed by decreasing order by waterchloroform and ethyl acetate fractions The same order ofactivity was observed in the ability of these fractions to reducecardiac arginase with 117 reduction for n-butanol fractionand to raise serum nitric oxide with 55 elevation for n-butanol fraction in mice orally administrated 250mgkg offractions for 21 days Arginase was found to be a diagnosticindicator for cardiovascular diseases including hypertension[62] Enhanced activity of nitric oxide is a critical factorto reduce the vascular resistance and blood pressure thatincreased in hypertensive rats and humans [63 64] Cardiacarginase reduction vasorelaxation antiatherogenic eventsand nitric oxide (NO) elevation were found to be responsiblefor antihypertensive activity of L micranthus Moderate andhigh abundance of steroids and terpenoids in n-butanol frac-tion strongly suggested that these phytoconstituents couldbe responsible for observed vasorelaxant and antiatherogenicactivity of n-butanol fraction Iwalokun and colleagues [30]have reviewed the possible mechanisms of antihypertensiveactivity of L micranthus

35 Antioxidant Activity The role of free radicals in manydiseases has been proven by recent developments in biomed-ical sciences Cellular damage caused by free radicals is pos-sibly responsible for many degenerative diseases includingheart disease cancer brain dysfunction and immune system

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 7: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Evidence-Based Complementary and Alternative Medicine 7

decline [65] Phenolic compounds are potent scavengers offree radicals [66] The antioxidant activity of compounds 1ndash11 isolated frommethanol extracts ofLmicranthus leafy twigswas investigated by 22-diphenyl-1-picrylhydrazyl (DPPH)assay All the tested compounds revealed significant antiox-idant effect (IC

50= 238ndash501 120583M) compared to chlorogenic

acid as a positive control (IC50

= 679 120583M) Compounds 10and 11 exhibited the most significant antioxidant activity [12]The results of DPPH assay on compounds 12ndash14 revealedsignificant antioxidant potentials with EC

50of 5542 5845

and 5971mgmL respectively compared to ascorbic acid asa positive control with EC

50= 176mgmL [22]

36 Antidiarrhoeal Activity Diarrhoea due to the risk ofsever potentially fatal dehydration can be a serious compli-cation in infants and elderly people [67] About 22 millionpeople mostly infants and children below 5 years are victimsof diarrhea annually [68] Because of the adverse effects ofsome existing antimotility medicines after prolonged usemany studies have been done for an alternative remedyamong traditional medicinal herbs [69 70] In vivo studyon methanolic extract of L micranthus leaf harvested fromsix different host trees including P americana B nitidaK acuminata P macrophylla C sinensis and I gabonensisindicated antimotility effect in rats with castor-oil-induceddiarrhoea Methanolic extract of L micranthus parasitic onP macrophylla (200mgkg) showed the most significantdecrease on defecation (9333) 4 hours after administrationcompared to atropine sulphate (2mgkg) as a positive control(80) It also significantly inhibited gastrointestinal transit by676 which is more than atropine sulphate (264) [9]

37 Hypolipidemic Activity The serum lipid analysis in miceorally was administered with 250mgkg of n-butanol chlo-roform ethyl acetate and water fractions of the methanolicextract of L micranthus harvested from K acuminata for 21days indicated with decrease in cholesterol and triglyceridewith the highest activity for n-butanol fraction Resultsdemonstrated lower total cholesterol triglycerides (TAG)and LDL-cholesterol levels particularly for n-butanol andwater fractions after 21 days without significant changes forHDL-cholesterol On day 21 n-butanol fraction significantlyreduced TAG level (1385 plusmn 34 versus 1528 plusmn 06mgdL)Total cholesterol and LDL-cholesterol levels also reducedfrom 1143 plusmn 35mgdL to 919 plusmn 04mgdL and from 422 plusmn43mgdL to 237 plusmn 09mgdL by n-butanol fraction on theday 21 respectively [30]

4 Conclusion

The overview of scientific investigations on L micranthusshowed various biological activities for this plant The phyto-chemical constituents and the activity of themedicinal valuesof L micranthus are strongly dependent on harvesting seasonand host species trees Phytochemicals and compounds iso-lated from L micranthus are in interest for the further inves-tigations towards application of this plant as anti-diabeticantibacterial antihypertensive hypolipidemic antioxidant

antidiarrhoeal and immunomodulatory medicines Furtherin vivo genotoxic tests of this plant can be also beneficial forthe safety approval for therapeutic applications

Conflict of Interests

All authors declared that there is no actual or potentialconflict of interests including any financial personal or otherrelationships with other people or organizations that couldinappropriately influence or be perceived to influence theirwork

Acknowledgment

The authors thank the Ministry of Higher Education(MOHE) Malaysia for High Impact Research (HIR) MOHEGrant (E000013-20001) They also would like to thank theUniversity of Malaya for University Malaya Research Grant(UMRG) (RG383-11HTM)

References

[1] P Griggs ldquoMistletoe myth magic and medicinerdquo The Bio-chemist vol 13 pp 3ndash4 1991

[2] N Nwude and M A Ibrahim ldquoPlants used in traditionalveterinary medical practice in Nigeriardquo Journal of VeterinaryPharmacology andTherapeutics vol 3 no 4 pp 261ndash273 1980

[3] E Kafaru ldquolsquoMistletoemdashan example of an all-purpose herbrsquoHerbal Remediesrdquo Guardian Newspaper vol 3 p 11 1993

[4] T Fukunaga I Kajikawa K Nishiya K Takeya andH ItokawaldquoStudies on the constituents of Japanese mistletoes from dif-ferent host trees and their antimicrobial and hypotensivepropertiesrdquo Chemical and Pharmaceutical Bulletin vol 37 no6 pp 1543ndash1546 1989

[5] R Scheer A Scheffler and M Errenst ldquoTwo harvesting timessummer and winter are they essential for preparing pharma-ceuticals from mistletoe (Viscum album)rdquo Planta Medica vol58 no 7 pp 594ndash599 1992

[6] D K Obatomi E O Bikomo and V J Temple ldquoAnti-diabeticproperties of the African mistletoe in streptozotocin-induceddiabetic ratsrdquo Journal of Ethnopharmacology vol 43 no 1 pp13ndash17 1994

[7] M L Wagner T Fernandez E Alvarez R A Ricco SHajos and A A Gurni ldquoMicromolecular and macromolecularcomparison of Argentina mistletoe (Ligaria cuneifolia) andEuropean mistletoe (Viscum album L)rdquo Acta FarmaceuticaBonaerense vol 15 no 2 pp 99ndash108 1996

[8] F H Ali T N Intesar W A Khylood and A H SaadldquoHematopoietic toxicity of Loranthus europaeus chloroformextract in vitro studyrdquo International Journal of ComprehensivePharmacy vol 17 pp 345ndash352 2005

[9] P O Osadebe C C Abba andMO Agbo ldquoAntimotility effectsof extracts and fractions of EasternNigeriamistletoe (Loranthusmicranthus Linn)rdquo Asian Pacific Journal of Tropical Medicinevol 5 no 7 pp 556ndash560 2012

[10] P O Osadebe and E O Omeje ldquoComparative acute toxicitiesand immunomodulatory potentials of five Eastern Nigeriamistletoesrdquo Journal of Ethnopharmacology vol 126 no 2 pp287ndash293 2009

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 8: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

8 Evidence-Based Complementary and Alternative Medicine

[11] B Oliver-Bever Medicinal Plants in Tropical West AfricaCambridge University Press New York NY USA 1986

[12] MOAgboD Lai F B COkoye POOsadebe andP ProkschldquoAntioxidative polyphenols from Nigerian mistletoe Loranthusmicranthus (Linn) parasitizing on Hevea brasiliensisrdquo Fitoter-apia vol 86 pp 78ndash83 2013

[13] A L Davis Y Cai A P Davies and J R Lewis ldquo1H and 13CNMR assignments of some green tea polyphenolsrdquo MagneticResonance in Chemistry vol 34 no 11 pp 887ndash890 1996

[14] P Fan H Lou W Yu D Ren B Ma and M Ji ldquoNovel flavanolderivatives from grape seedsrdquo Tetrahedron Letters vol 45 no15 pp 3163ndash3166 2004

[15] A Gramza and J Korczak ldquoTea constituents (Camellia sinensisL) as antioxidants in lipid systemsrdquo Trends in Food Science andTechnology vol 16 no 8 pp 351ndash358 2005

[16] M Singh M Arseneault T Sanderson V Murthy and CRamassamy ldquoChallenges for research on polyphenols fromfoods in Alzheimerrsquos disease bioavailability metabolism andcellular andmolecularmechanismsrdquo Journal of Agricultural andFood Chemistry vol 56 no 13 pp 4855ndash4873 2008

[17] M M Manir J K Kim B-G Lee and S-S Moon ldquoTeacatechins and flavonoids from the leaves of Camellia sinensisinhibit yeast alcohol dehydrogenaserdquo Bioorganic and MedicinalChemistry vol 20 no 7 pp 2376ndash2381 2012

[18] L Sanchez-del-Campo FOton A Tarraga J Cabezas-HerreraS Chazarra and J N Rodrıguez-Lopez ldquoSynthesis and bio-logical activity of a 345-trimethoxybenzoyl ester analogue ofepicatechin-3-gallaterdquo Journal of Medicinal Chemistry vol 51no 7 pp 2018ndash2026 2008

[19] O A Eldahshan ldquoIsolation and structure elucidation of phe-nolic compounds of carob leaves grown in Egyptrdquo CurrentResearch Journal of Biological Sciences vol 3 pp 53ndash55 2011

[20] M Materska and I Perucka ldquoAntioxidant activity of the mainphenolic compounds isolated from hot pepper fruit (Capsicumannuum L)rdquo Journal of Agricultural and Food Chemistry vol53 no 5 pp 1750ndash1756 2005

[21] E N Frankel A L Waterhouse and P L Teissedre ldquoPrincipalphenolic phytochemicals in selected California wines and theirantioxidant activity in inhibiting oxidation of human low-density lipoproteinsrdquo Journal of Agricultural and Food Chem-istry vol 43 no 4 pp 890ndash894 1995

[22] E O Omeje O P Ogoamaka A Kawamura et al ldquoThreemdash(minus) catechin-o-rhamnosides from the Eastern Nigeria mistletoewith potent immunostimulatory and antioxidant activitiesrdquoBiomolecules vol 1 no 1 pp 1ndash6 2012

[23] E O Omeje P O Osadebe C O Esimone C S Nworu AKawamura and P Proksch ldquoThree hydroxylatedlupeol-basedtriterpenoid esters isolated from the Eastern Nigeria mistletoeparasitic on Kola acuminatardquoNatural Product Research vol 26no 19 pp 1775ndash1781 2012

[24] O E Ogechukwu O P Ogoamaka N C Sylvester et alldquoSteroids and triterpenoids from Eastern Nigeria mistletoeLoranthus micranthus Linn (Loranthaceae) parasitic on Kolaacuminata with immunomodulatory potentialsrdquo Phytochem-istry Letters vol 4 no 3 pp 357ndash362 2011

[25] P Osadebe E Omeje A Kawamura and F Okoye ldquoLupeolderivatives from the Eastern Nigeria mistletoe Loranthusmicranthus Linn (Loranthaceae) with enhanced cell prolifera-tive potentialsrdquo Planta Medica vol 76 article 091 2010

[26] E Omeje P Osadebe P Procksh et al ldquoImmunomodulatoryand antioxidant constituents of Eastern Nigeria mistletoe

Loranthus micranthus Linn (Loranthaceae) parasitic on Colaacuminata Schott et Endlrdquo Planta Medica vol 76 p 129 2010

[27] E O Omeje P O Osadebe C S Nworu et al ldquoA novelsesquiterpene acid and an alkaloid from leaves of the EasternNigeria mistletoe Loranthus micranthuswith potent immunos-timulatory activity on C57BL6 mice splenocytes and CD69moleculerdquo Pharmaceutical Biology vol 49 no 12 pp 1271ndash12762011

[28] P O Osadebe E O Omeje S C Nworu et al ldquoAntidiabeticprinciples of Loranthus micranthus Linn parasitic on PerseaamericanardquoAsian Pacific Journal of TropicalMedicine vol 3 no8 pp 619ndash623 2010

[29] P O Osadebe E O Omeje P F Uzor E K David and DC Obiorah ldquoSeasonal variation for the antidiabetic activity ofLoranthus micranthus methanol extractrdquo Asian Pacific Journalof Tropical Medicine vol 3 no 3 pp 196ndash199 2010

[30] B A Iwalokun S A Hodonu S Nwoke O Ojo and P UAgomo ldquoEvaluation of the possible mechanisms of antihyper-tensive activity of Loranthus micranthus an african mistletoerdquoBiochemistry Research International vol 2011 Article ID 1594399 pages 2011

[31] P O Osadebe and S E Ukwueze ldquoA comparative study ofthe phytochemical and anti-microbial properties of the EasternNigerian specie of African Mistletoe (Loranthus micranthus)sourced from different host treesrdquo Bio-Research vol 2 no 1 pp18ndash23 2004

[32] P O Osadebe G B Okide and I C Akabogu ldquoStudy on anti-diabetic activities of crude methanolic extracts of Loranthusmicranthus (Linn) sourced from five different host treesrdquoJournal of Ethnopharmacology vol 95 no 2-3 pp 133ndash1382004

[33] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoPlanta Medica vol 73 pp 205ndash210 2007

[34] L M Perry and J Metzger Medicinal Plants of East andSouth East Asia Attributed Properties and Uses MIT PressCambridge Mass USA 1980

[35] D O Edem and I F Usoh ldquoBiochemical changes inWistar ratson oral doses of mistletoe (Loranthus micranthus)rdquo AmericanJournal of Pharmacology and Toxicology vol 4 no 3 pp 94ndash972009

[36] B A Iwalokun A O Oyenuga G M Saibu GM and JAyorinde ldquoAnalyses of cytotoxic and genotoxic potentials ofLoranthus micranthus using the Allium cepa testrdquo CurrentResearch Journal of Biological Sciences vol 3 no 5 pp 459ndash4672011

[37] H M Kim S B Han G T Oh et al ldquoStimulation of humoraland cellmediated immunity by polysaccharide frommushroomPhellinus linteusrdquo International Journal of Immunopharmacol-ogy vol 18 no 5 pp 295ndash303 1996

[38] C K Ameho A A Adjei K Yamauchi et al ldquoModulation ofage-related changes in immune functions of protein-deficientsenescence-accelerated mice by dietary nucleoside-nucleotidemixture supplementationrdquo British Journal of Nutrition vol 77no 5 pp 795ndash804 1997

[39] L A Ande ldquoMistletoe the magic herbrdquo Pharmacology Journalvol 229 pp 437ndash439 1982

[40] E Juanita ldquoMistletoe good for more than free kissesrdquo Journalof American Botanical Council vol 68 pp 50ndash59 2005

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 9: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Evidence-Based Complementary and Alternative Medicine 9

[41] P O Osadebe and E O Omeje ldquoIsolation and characterisationof antiviral and immunomodulatory constituents from Nige-rian mistletoe Loranthus micranthusrdquo Planta Medica vol 73p 108 2007

[42] P O Osadebe and E O Omeje ldquoImmunomodulatory activitiesof n-hexane and methanol extracts of Loranthus micranthusLinn parasitic on Parkia biglobosardquo Planta Medica vol 74article 217 2008

[43] P O Osadebe and E O Omeje ldquoPreliminary fractionationindicates that flavonoids steroids and terpenoids are themain immunomodulatory constituents of Loranthus micran-thus (Linn)rdquo Planta Medica vol 75 article 78 2009

[44] O E Ogechukwu O P Ogoamaka N C Sylvester A Kawa-mura and P Proksch ldquoImmunomodulatory activity of a lupanetriterpenoid ester isolated from the eastern Nigeria mistletoeLoranthus micranthus (Linn)rdquo Asian Pacific Journal of TropicalMedicine vol 4 no 7 pp 514ndash522 2011

[45] S H Lee and Y J Jeon ldquoAnti-diabetic effects of brown algaederived phlorotannins marine polyphenols through diversemechanismsrdquo Fitoterapia vol 86 pp 129ndash136 2013

[46] R A DeFronzo ldquoPharmacologic therapy for type 2 diabetesmellitusrdquo Annals of Internal Medicine vol 131 no 4 pp 281ndash303 1999

[47] I C Uzochukwu and P O Osadeb ldquoComparative evaluation ofantidiabetic activities of flavonoids extract and crude methanolextract of Loranthus micranthus parasitic on Kola acuminatardquoJournal of Pharmaceutical and Allied Sciences vol 4 no 1 pp2ndash7 2007

[48] Z J Wang Z Q Yang T N Huang L Wen and Y W LiuldquoExperimental research on inhibitory effect of alcohol extractsfrom Loranthus yadoriki Sieb on coxsackie B3 virusrdquo ZhongguoZhong Yao Za Zhi vol 25 no 11 pp 685ndash687 2000

[49] Y-K Kim S K Young U C Sang and Y R Shi ldquoIsolationof flavonol rhamnosides from Loranthus tanakae and cytotoxiceffect of themonhuman tumor cell linesrdquoArchives of PharmacalResearch vol 27 no 1 pp 44ndash47 2004

[50] O Z Ameer I M Salman M J A Siddiqui et al ldquoCharacter-ization of the possible mechanisms underlying the hypotensiveand spasmogenic effects of Loranthus ferrugineus methanolicextractrdquo American Journal of Chinese Medicine vol 37 no 5pp 991ndash1008 2009

[51] P Abirami M Gomathinayagam and R Panneerselvam ldquoPre-liminary study on the antimicrobial activity of Enicostemma lit-torale using different solventsrdquo Asian Pacific Journal of TropicalMedicine vol 5 no 7 pp 552ndash555 2012

[52] P O Osadebe and I C Akabogu ldquoAntimicrobial activity ofLoranthusmicranthus harvested from kola nut treerdquo Fitoterapiavol 77 no 1 pp 54ndash56 2006

[53] E A C Cemaluk and N N Emeka ldquoPhytochemical propertiesof some solvent fractions of petroleum ether extract of theAfrican mistletoe (Loranthus micranthus Linn) leaves and theirantimicrobial activityrdquo African Journal of Biotechnology vol 11no 62 pp 12595ndash12599 2012

[54] P O Osadebe C A Dieke and F B C Okoye ldquoA study ofthe seasonal variation in the antimicrobial constituents of theleaves of Loranthusmicranthus sourced from Percia americanardquoResearch Journal ofMedicinal Plant vol 2 no 1 pp 48ndash52 2008

[55] S E Ukwueze and POOsadebe ldquoDetermination of anti-fungalproperties of the african mistletoe species Loranthus micran-thus Lrdquo International Journal of Pharma and Bio Sciences vol3 no 1 pp 454ndash458 2012

[56] S E Ukwueze P O Osadebe and N O Ezenobi ldquoBioassay-guided evaluation of the antibacterial activity of Loranthusspecies of the African mistletoerdquo International Journal of Phar-maceutical and Biomedical Research vol 4 no 2 pp 79ndash822013

[57] J Fry ldquoDeaths and complications from hypertensionrdquo Journalof the Royal College of General Practitioners vol 25 no 156 pp489ndash494 1975

[58] P A Meredith ldquoCandesartan cilexetilmdasha review of effects oncardiovascular complications in hypertension and chronic heartfailurerdquoCurrentMedical Research andOpinion vol 23 no 7 pp1693ndash1705 2007

[59] G Y Yeh D M Eisenberg T J Kaptchuk and R S PhillipsldquoSystematic review of herbs and dietary supplements forglycemic control in diabetesrdquo Diabetes Care vol 26 no 4 pp1277ndash1294 2003

[60] O C Amira and N U Okubadejo ldquoFrequency of comple-mentary and alternative medicine utilization in hypertensivepatients attending an urban tertiary care centre in NigeriardquoBMCComplementary andAlternativeMedicine vol 7 article 302007

[61] D K Obatomi V O Aina and V J Temple ldquoEffects ofAfrican mistletoe extract on blood pressure in spontaneouslyhypertensive ratsrdquo Pharmaceutical Biology vol 34 no 2 pp124ndash127 1996

[62] C Demougeot A Prigent-Tessier C Marie and A BerthelotldquoArginase inhibition reduces endothelial dysfunction and bloodpressure rising in spontaneously hypertensive ratsrdquo Journal ofHypertension vol 23 no 5 pp 971ndash978 2005

[63] J G Umans and R Levi ldquoNitric oxide in the regulation of bloodflow and arterial pressurerdquo Annual Review of Physiology vol 57pp 771ndash790 1995

[64] C-C Wu and M-H Yen ldquoHigher level of plasma nitricoxide in spontaneously hypertensive ratsrdquo American Journal ofHypertension vol 12 no 5 pp 476ndash482 1999

[65] O I Aruoma ldquoFree radicals oxidative stress and antioxidantsin human health and diseaserdquo Journal of the American OilChemistsrsquo Society vol 75 no 2 pp 199ndash212 1998

[66] M K Zainol A Abd-Hamid S Yusof and R Muse ldquoAntiox-idative activity and total phenolic compounds of leaf root andpetiole of four accessions of Centella asiatica (L) Urbanrdquo FoodChemistry vol 81 no 4 pp 575ndash581 2003

[67] G F LongstrethW GThompsonW D Chey L A HoughtonF Mearin and R C Spiller ldquoFunctional bowel disorderrdquoGastroenterology vol 130 no 5 pp 1480ndash1491 2006

[68] N Venkatesan V Thiyagarajan S Narayanan et al ldquoAnti-diarrhoeal potential of Asparagus racemosus wild root extractsin laboratory animalsrdquo Journal of Pharmacy and PharmaceuticalSciences vol 8 no 1 pp 39ndash45 2005

[69] J D Gale ldquoThe use of novel promotility and prosecretoryagents for the treatment of chronic idiopathic constipationand irritable bowel syndrome with constipationrdquo Advances inTherapy vol 26 no 5 pp 519ndash530 2009

[70] S Rajan H Suganya T Thirunalasundari and S JeevaldquoAntidiarrhoeal efficacy of Mangifera indica seed kernel onSwiss albino micerdquo Asian Pacific Journal of Tropical Medicinevol 5 no 8 pp 630ndash633 2012

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 10: Review Article Loranthus micranthus Linn.: Biological Activities …downloads.hindawi.com/journals/ecam/2013/273712.pdf · 2019-07-31 · Review Article Loranthus micranthus Linn.:

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom