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www.wjpps.com Vol 6, Issue 8, 2017. 2418 Qazi et al. World Journal of Pharmacy and Pharmaceutical Sciences ETHNOBOTANY AND THERAPEUTIC POTENTIAL OF KABAB CHINI (PIPER CUBEBA) Dr. Qazi Zaid Ahmad*, Aziz Ur Rahman and Tajuddin Department of Saidla, Faculty of Unani Medicine, AMU, Aligarh-202002, UP, India. ABSTRACT Kabab chini (Piper cubeba) the dried ripe berries of Piper cubeba commonly known as Cubeb which has been used in traditional medicines for various disorders. Such as urogenital diseases, gonorrhoea, dysentery, syphilis, abdominal pain, diarrhoea, enteritis and asthma. It has been described in the classical Unani literature in detail and various actions such as Mudirre baul (diuretic), Mufattit wa Mukhrije Hasat (lithotriptic), Dafeye taffun (antiseptic), Muqa-wwiye Kulyah (kidney tonic), Mohafize Kulyah (nephroprotective), etc. have been ascribed to it. In recent years the Kabab chini (Piper cubeba) has been studied by a number of scientists to validate the acclaimed medicinal properties along with pharmacogonostical and phytochemical properties. So an attempt has been made for review of the work carried out by scientific community along with an overview on ethnobotantical and ethnopharmcological description. KEYWORDS: Mudirre baul, Mufattit wa Mukhrije Hasat, Dafeye taffun etc. INTRODUCTION Kabab Chini is the dried ripe berries of Piper cubeba. Piper is the nominate genus of the family Piperaceae. A pan tropical family composed of five to eight or more genera. The two largest genera are Piper and Peperomia, each containing about one thousands species, thirty species are medicinal in Asia-Pacific. [1, 2] Members of the genus Piper are used for many purposes, such as foods and spices, fish bait, fish poison, hallucinogen, insecticides, oils, ornaments, perfumes and for many medicines. [3,4] Article Received on 19 June 2017, Revised on 10 July 2017, Accepted on 31 July 2017, DOI: 10.20959/wjpps20178-9870 *Corresponding Author Dr. Qazi Zaid Ahmad Department of Saidla, Faculty of Unani Medicine, AMU, Aligarh- 202002, UP, India. WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES SJIF Impact Factor 6.647 Volume 6, Issue 8, 2418-2436 Review Article ISSN 2278 – 4357

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Qazi et al. World Journal of Pharmacy and Pharmaceutical Sciences

ETHNOBOTANY AND THERAPEUTIC POTENTIAL OF KABAB

CHINI (PIPER CUBEBA)

Dr. Qazi Zaid Ahmad*, Aziz Ur Rahman and Tajuddin

Department of Saidla, Faculty of Unani Medicine, AMU, Aligarh-202002, UP, India.

ABSTRACT

Kabab chini (Piper cubeba) the dried ripe berries of Piper cubeba

commonly known as Cubeb which has been used in traditional

medicines for various disorders. Such as urogenital diseases,

gonorrhoea, dysentery, syphilis, abdominal pain, diarrhoea, enteritis

and asthma. It has been described in the classical Unani literature in

detail and various actions such as Mudirre baul (diuretic), Mufattit wa

Mukhrije Hasat (lithotriptic), Dafeye taffun (antiseptic), Muqa-wwiye

Kulyah (kidney tonic), Mohafize Kulyah (nephroprotective), etc. have

been ascribed to it. In recent years the Kabab chini (Piper cubeba) has

been studied by a number of scientists to validate the acclaimed

medicinal properties along with pharmacogonostical and phytochemical properties. So an

attempt has been made for review of the work carried out by scientific community along with

an overview on ethnobotantical and ethnopharmcological description.

KEYWORDS: Mudirre baul, Mufattit wa Mukhrije Hasat, Dafeye taffun etc.

INTRODUCTION

Kabab Chini is the dried ripe berries of Piper cubeba. Piper is the nominate genus of the

family Piperaceae. A pan tropical family composed of five to eight or more genera. The two

largest genera are Piper and Peperomia, each containing about one thousands species, thirty

species are medicinal in Asia-Pacific.[1, 2]

Members of the genus Piper are used for many purposes, such as foods and spices, fish bait,

fish poison, hallucinogen, insecticides, oils, ornaments, perfumes and for many medicines.[3,4]

Article Received on 19 June 2017,

Revised on 10 July 2017, Accepted on 31 July 2017,

DOI: 10.20959/wjpps20178-9870

*Corresponding Author

Dr. Qazi Zaid Ahmad

Department of Saidla,

Faculty of Unani

Medicine, AMU, Aligarh-

202002, UP, India.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 6.647

Volume 6, Issue 8, 2418-2436 Review Article ISSN 2278 – 4357

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The berries of Piper cubeba, commonly known as Cubeb, have been extensively used as a

condiment, particularly in the tropics. Old Arabian and Persian Physician are said to have

used the fruit in genito-urinary diseases. Its use in the Western Medicine can be traced to the

middle ages.[5]

In Indonesia Piper cubeba is valued as a medicinal plant and used in

Indonesian traditional medicine to treat gonorrhoea, dysentery, syphilis, abdominal pain,

diarrhoea, enteritis and asthma.[6]

Historical Aspect

In the 4th century BC, Theophrastus mentioned komakon. Guillaume Budé and Claudius

Salmasius have identified komakon with cubeb, probably due to the resemblance which the

word bears to the Javanese name of cubeb, kumukus. This is seen as a curious evidence of

Greek trade with Java in a time earlier than that of Theophrastus.[7]

In India, Sanskrit texts included cubeb in various remedies. Charaka and Sushruta prescribed

a cubeb paste as a mouthwash, and the use of dried cubebs internally for oral and dental

diseases, loss of voice, halitosis, fevers, and cough.[8]

In the Raja Nirghanta which was

written 600 years ago cubebs appear in the name of kankola.[8]

Unani physicians use a paste

of the cubeb berries externally on male and female genitals to intensify sexual pleasure

during coitus. Due to this attributed property, cubeb was called "Habb-ul-Uruus".[9]

Cubeb was introduced into medicine by the Arab physician of the middle ages. Masoodi in

10th century stated them to be a production of Java. The author of pharmacographia draw

attention to the fact that the action of Cubebs upon the urogenital organs, though known to

the old Arabian physicians were unknown to modern European writers on materia medicas at

the commencement of the present century.[8]

Nicholas Culpeper wrote in the London

Dispensatorie that cubebs were "hot and dry in the third degree, they cleanse the flegm of

head and strenghthen the brain, they heat the stomach and provoke lust".[10]

The National

Botanic Pharmacopoeia printed in 1921 tells that cubebs were "an excellent remedy for flour

albus or whites.[11]

Etymology

The Greek physician and botanist Dioscorides author of Kitab ul Hashaish as cited by Razi,

mentioned it by the name of kasifiyoon and the some other Unani physicians named it

Safra’anioon and Maharioon and in Greek it was famous by the name of Qarqisoon, Jalinoos

mentioned it in his book “Kitabul Advia al Muqablatu lil Adwa” by the name of

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Qaraisoon.[12,13]

The word cubeb entered European language via Arabic, Al-kababah, which,

however, is of unknown origin but Zakaria Razi mentioned in his book Al-Havi that the

Hunain named it Kababah.[12]

Kababah is Arabic word and it is also known in Arabic by

"Habb-ul-Uruus" and in Unani by the name of Qaqnoon, Qarfasyoon, Qarqasyoon,

Qraqisoon, and in Roman language by the name of Diflyoon.[13,14]

Vernacular Names

Arabic: Kabaaba, Kababah, "Habb-ul-Uruus"

Chinese: Biji, Bicheng qie Czech

English: Jawa peppercorn, Jawanese pepper, Tailed Pepper

Hindi: Kabab-chini, Sital chini

Indonesian Cabé jawa, Kamukus

Japanese: Kubeba, Kubebu

Korean: Chaba huchu, Jaba huchu, Kubepu Kyubebu

Persian: Kubabah, Kubabah

Russian: Perets Kubeba, Yavanskij perets, Perets kubebe

Turkish: Hint biberi tohomu, Java biberi, Kübabe,

Urdu: Kabab chini.[12,13,14,15]

Habitat and Distribution

Piper cubeba (Piperaceae) inhabits Java, Sumatra, Southern Borneo, Molucc and other isles

in the Indian Ocean. It is mostly grown in Java and Sumatra, hence some time known as

“Java pepper” but also from some African countries (SierraLeone, Congo), cubeb pepper is

exported. It is cultivated in some of the West Indian islands.[16]

Efforts have been made to

cultivate it in India, mostly in Mysore but not on a commercial scale. Cubeb can be easily

grown by planting at the foot of the shade trees in coffee plantation. The fruits are collected

when fully grown but still green, and dried in the sun when they become black and

wrinkled.[17]

Description of Drug in Unani Literature

Morphology

The morpholgy has been described in detail by certain Unani physicians. Zakaria Razi

mentioned in Al-Havi that the fruit of Kababah is similar to black pepper. Pungent and bitter

in taste with pleasant odour and its property are similar to that of Fuwwah and Darchini but

Darchini is more efficacious.[12]

Ishaq bin Imran mentioned that its "Habb-ul-Uruus" and its

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properties are just like pepper, it has a tail or pedicle on its base which is whitish yellow in

colour. Ibn Haitham ascribed that it has two types.

1. Long

2. Short

The long type is "Habb-ul-Uruus" and the shorter one is known as Flanja. Hunain and other

translaters cited that the Bitrique told about the Greek name of Kabab chini is Qarqisoon and

Hunain named it Kababah. Jalinoos mentioned in his book Kitab al Advia al that the

Qarqisoon is the thin pieces of wood as Darchini, while the kababah found in the form of fruit

(Habb) however may be these thin pieces of wood from this fruit.[12,14]

Abu Haneefah

ascribed that the tree of Kababah just as tree of Aas and the leaves are thin as compared to

leaves of Raihan, the flower is whitish yellow and grown into the hard soil. The fruit is

globular or oval shaped and the diameter is about 1/6 inch long blackish brown in colour,

wrinkled surface and having stalk or tail on its back side, beneath the wrinkled surface hard

and brown covering having seeds when fruit is full riped. It possesses pungent and some what

bitter taste with a strong characteristic aromatic odour. The stalked berries are a little bit

larger than pepper corns, having a furrowed surface. Most berries are hollow. They are sold

whole and should be crushed or ground before usage. The powder of Kababah is reddish

brown having characteristic sharp and pleasant odour.[18]

Amanullah khan mentioned in his book “Ganj Bad Award” that the kababah has three

varities:

1. Habashi

2. Chini

3. Hindi

The difference between them according to their shape or morphology is that the variety of

kababah which belongs to China has small fruit as compare to other species, a little longer

than the black pepper having a stalk on their head, hollow and light in weight. The fruit of

kababah habashi is bigger and heavier than the Chinese variety. It is filled internally and one

of the corners is white and has characteristic pleasant odour while the taste of both is similar.

The variety which belongs to India is rounded, bigger and heavier than the variety of China,

after crushing it gives the characteristic aroma and internally white in colour and it does not

have the stalk.[12,14,18]

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Hakim Momin khan described in his book, Tohfat ul Mominin that the fruit of kababah is just

as Habbe Balsan. Its aroma is also similar to the same fruit, blackish in colour, the pulp is

white and the tree is similar with the tree of Maurid and in India its small variety is found

which is known as Flanja.[19]

Hakim Ali bin Husain Ansari mentioned about the Kababah,

(Habbul-Uruus) that it has the property of Fuwwah.[20]

Daud Zurair Antaki mentioned in his book that the tree of kababah is similar to the tree of

Aas and has two types:

(1) Kabir: It is just like Habbe balsan having white pulp.

(2) Saghir: It is known as Falanjah and is of better quality which has pleasant odour. Its

efficacy tends to remain upto 10 years.[21]

Mizaj (Temperament)

Hot and dry in second degree.[8]

Masih bin Hakam said that it has both the hot and cold temperament but the hotness

dominantes.[18,22]

Af’aal (Pharmacological Actions)

Kabab chini (Piper cubeba) is described extensively in classical Unani literature, and various

actions of the plant have been discussed. Some pharmacological actions are as follows:

Munaqq-e- kulyah wa masanah (Cathartic for kidney and bladder), Mudirr-e- baul (Diuretic),

Mukhrij-e- sang-e- gurdah wa masanah (Lithotriptic), Mufattih-e- sudad (Deobstruent),

Mulattif (Demulcent), Habis-e- ishal (Astringent), Dafa-e- taaffun (Anti septic),Mufattih-e-

sudad-e- jigar (Deobstruent), Muqavvi-e- jigar (Hepatotonic) Muhallil (Anti inflammatory),

Mutayyib-e- dahan (Mouth Refreshner), Muharrik (Stimulant), Nafey-e Zeeq un nafas (Anti

asthmatic),Kasir-e-riyah(Carminative),Musakkin(Sedative),Muqawwi-e

me’adah(Gastrotonic).[12,14,18,21]

Medicinal uses

Qurooh lissa mutaffnah (Septic gingivitis), Qulae dahan mutaffina (Septic stomatitis)

Quroohe majara baul (Uro-genital ulcer), Yarqan (Jaundice),Qurooh lissa (Gums ulcer),

Fasade maedah wa tahal (Disorders of stomach and spleen),Riyah wa hasaat (Gases and

calculi),Waram (Inflammation), Khafqan (Palpitation), Hasate gurdah wa masana (Kidney

and Bladder calculi), Suda’ (Headache), Quroohe fam (Mouth/oral ulcer), Buae dahan

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(Halitosis) Sudda-e- jigar (Hepatic obstruction),Amraz Alate Tanasul wa Baul (Genito

urinary disease), Iltehabe Masana (Cystitis), Suzak (Gonorrhoea), Zaheer (Dysentery),

Waj’ul Mafasil (Rheumatism),Sual (Cough) Qurooh (Ulcers), Ehtebase Baul (Retention of

urine).[12,14,18,21]

Mazarrat (Adverse effect) Headache, Indigestion.[18,21]

Musleh (corrective) In case of adverse effect of Kabab chini the following drugs are used as

musleh (corrective).

Mastagi (Pistacia lentiscus)

Sandal safaid (Santalum album)

Gule surkh177,164,175 (Rosa damascus)

Miqdare khoorak (Dose)

3 - 4 ½ gm (powder form)

1 to 3 gm[19]

4 gm[23]

5 gm[24]

9 gm (decoction)[12]

5-20 drops (Roghan),[12,18]

Important Farmulations

Jawarish Zarooni

Laboobe Sagheer,

Majoone Seer Alvi Khan

Majoone Antaki

Sufoofe Shora murakkab

Sufoofe Indrijulab

Sinoone mujalli

Zuroore Qula’ Abyaz

Zuroore[23,24]

Description of the Drug in Modern literature

Classification

Taxonomy

Kingdom : Plantae.

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Division : Magnoliophyta.

Class : Magnoliopsida.

Order : Piperales.

Family : Piperaceae.

Genus : Piper.

Species : P. cubeba.

In field collection Piperaceae can be recognized by three main features.

Articulate stem

Asymmaterical or cordate leaves

And axillary spikes of little round berry like fruits.

Macroscopic features

Piper cubeba, a climbing shrub with cylindrical, smooth zigzag, striate stem some what

thickened at the node. Fruit wrinkled, rounded, 5-7 mm in diameter, light brown to dark

brown, about 7 mm long stalk attached, pericarp red to slightly brown, testa fused with

pericarp, fruit hard and stony albumen white and oily, odour aromatic and characteristic, taste

pungent and slightly bitter.[24,25]

The fruit is almost globular (diameter 3-6 mm.) with a

slender stalk like portion (length, upto 7 mm.) attached to its base, hence the Cubeb is also

known as Tailed pepper. The pericarp is dusky red to slightly brown, rarely grayish in

colour.[26]

In size and form Cubeb resembles black pepper, but they are readily distinguished

from it by being furnished with stalk, from which circumstance they have received the name

of tailed pepper. They are spherical in form, and about the size generally of black pepper, or

small pea; their colour is blackish or grayish.[16]

It climbes to 10 feet high, it has heart- to

lance shaped leaves up to 6 inch and 4 inch flower spike.[17]

The distinguishing feature being

the short pedicle or stalk attached to the base of the cubebs. The stalk is 4-7 mm long.[23]

Leaves: Alternate, on short stout petiole, blade about 6 inches long, lanceolate or oval

oblong, tapering to the acute apex, usually somewhat unequal at the base, quite entire,

slightly wavy, glabrous on both surfaces, somewhat coriaceous, deep green rather paler and

prominent vein beneath.[16,23]

Flower: Unisexual, dioecioues, minute, sessile, each with a bract at the base, densly crowded

in small, cylindrical, stalked, solid spike coming of opposite the leaves; the mail spikes

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slender, tapering, shortly stalked, about an inch long, the female shorter, blunt, thick and

fleshy, on longer stalks.[16,23]

Fruit: Globular smooth, about ¼ inch long, with a blunt apiculous and tapering below into a

stalk –like base, which a little longer than round extremity, projecting horizontally from the

axis and together forming a lax raceme ( many of the ovaries becoming abortive) about 2

inches long.[16,23]

Other species of Piper which are commonly being used as substitute or adulterants

Piper species yielding fruits of similar nature are: P. ribesioides Wall. and P. sumatrana DC.

Which are considered possibely as large forms of P. cubeba. Fruits of other species of Piper

like P. crassipes, Korth., P. cannaum, Blume. and P .baccatum, Blume are reported to be

used as substitutes or adulterants. Fruits obtained from P. clusii DC. and P. guineense, DC.

are also used as substitutes, they are often called false Cubebs and are obtained from Africa.

Fruits of Litsea cubeba, Pers. are also used as substitute. Adulteration of true cubebs with

similar fruits from other Piper spp. can be detected by visual examination, or under the

microscope, or by treatment with sulphuric acid with which the true fruits develop a bright

red color.[25]

Trade standards require that a given lot of cubebs should contain, shrivelled and

immature fruits >10; stems, >5; foreign organic matter, > 2; and acid-insoluble ash, >2%,

each 100 gm of the cubebs should yield not less than 13 ml of volatile oil.[25]

Leaves and Flowers of Kabab chini (Piper cubeba).

Fruits and flower of Kabab chini Piper cubeba.

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Microscopic features of the fruit

The pericarp consists of an epidermis beneath which is an interrupted row of small thick wall

cells. Within this, the parenchyma is composed of cells containing starch and oil, in the latter,

bundles of needle shaped crystals of Cubebin may be observed, lastly the innermost layer of

pericarp is formed by several rows of tangentially extended cells containing essential oil. The

nut is yellow and brittle. The seed when present is seen to contain crystals of Cubebin.

Transverse section of the fruit show an outer layer of epidermis, externally covered with thick

cuticle, arrow of 2-5 small, crushed, brown and thick walled cells below, mesocarp composed

of large thin- walled parenchymatous cells, oil cell and vascular bundle, endocarp of multi

layered sclerieds heavily lignified with narrow lumen, testa and gegman composed of

elongated cells, tegmen cells, hyaline and kernel cells grayish in colour.[8,23,24]

Description of Tissue from powdered: Cubeb (Piper cubeba).[23,27]

1. Lignified fiber 2. Perisperm 3. Thin wall perisperm 4. Starch grains

5. Spermoderm in surface view 6. Small calcium oxlate prisms

7. Spermoderm in section view 8. Yellowish brown wall.

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Phytochemical studies

The dried cubeb berries contain essential oil consisting monoterpenes (sabinene 50%, -

thujene, carene, 1,4-cineol and 1,8-cineol) and sesquiterpenes (caryophyllene, copaene, - and

-cubebene, "-cadinene, cubebol, germacrene). About 15% of a volatile oil is obtained by

distilling cubebs with water. Cubebene, the liquid portion, has the formula C15H24. It is a

pale green or blue-yellow viscous liquid with a warm woody, slightly camphoraceous

odour.[28]

After rectification with water, or on keeping, this deposits rhombic crystals of

camphor of cubebs (C15 H60). Rao, Sudborough and Watson (1925) have studied the oil

distilled from the cubebs experimentally grown there. They were able to obtain 11.85% of the

oil with the following constant; specific gravity 0.9167, optical rotation-29.9dig, refractive

index 1.4894, saponification value after acetylation.[29,30]

Cubebin is a crystalline substance existing in cubebs, discovered by Eugène Soubeiran and

Capitaine in 1839. It may be prepared from cubebene, or from the pulp left after the

distillation of the oil. The drug, along with gum, fatty oils, and malates of magnesium and

calcium, contains also about 1% of cubebic acid, and about 6% of a resin. A lignan-cubebin,

mp. 133 – isolated from fruits.[31]

Two new sesquiterpene hydrocarbons-

bicyclosesquiphellandrene and 1epibicyclosesqui-phellandrene-isolated from essential oil.[30]

Hexane extract of Piper cubeba seeds contained palmitic, linoleic, oleic, linolenic, stearic,

arachidic and behenic acids.[32]

(-)Clusin, (-) Cubebin, (-) dihydrocubebin, (-)hinokinin and

(2R, 3R)2-(3”, 4”, 5”-trimethoxybenzyl)-3-(3’, 4’-methylenedioybenzyl)-1,4-butanediol

isolated from fruit alpha-ethoxycubebin, beta-ethoxycubebin, dihydrocubebin monoacetate,

hetrotropan, magnosalin, 5”-methoxyhinokinin and 2,4,5-trimethoxybenzaldehyde

isolated.[33,34]

The lignan profiles of aerial part of Piper cubeba, was determined using GC,

MS and HPLC. The number of lignans found in the leaves was 15, followed by berries and

the stalks with respectively 13 and 5 lignans. Cubebin, hinokinin, yatein, isoyatein are

common lignans in the genus Piper and appeared as major components in all part of Piper

cubeba investigated. Piperine is an abundant alkaloid in the berries of this species.[35]

Twenty

four lignans have so far been reported from P. cubeba.[36,37,38,39,40,41]

Lignans are an important group of secondary metabolites that are also assumed to contribute

to the biological activity. Some of these lignans showed inhibitory activity against

cytochrome P450 enzymes that are involved in the metabolism of all currently used

drugs.[36,42]

Yatein, hinokinin, cubebin, dihydrocubebin have been reported to have

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Qazi et al. World Journal of Pharmacy and Pharmaceutical Sciences

antifeedant activity against a number of stored product insects. This activity is comparable to

podophyllotoxin.[43]

Hinokinin has been reported to have anti-inflammatory and analgesic

effect. Because of the structural relationship, hinokinin can be synthesized using cubebin as

Precursor.[44]

Cubebin has been shown to possess anti-inflammatory, analgesic and

trypanocidal activities.[44,45,46]

Yatein is also an interesting lignan due to its biological activity

and its function as a biosynthetic precursor of deoxypodophyllotoxin and podophyllotoxin

that are well known for their anticancer properties.

Pharmacological Studies

Antioxidant effect

Gayatri N et al, Had studied and examined the pyridine class alkaloid i.e. piperine is available

in rich amount in Piper nigrum and Piper cubeba having family of Piperaceae. It is

commonly used in preparation of various herbal cough syrups and used as anti malarial, anti

inflammatory and anti leukemia. Ethanol extract of Piper cubeba having high antioxidant

activity.[47]

Aboul-Enein HY et al, Had studied and examined Piper cubeba isolates for anti-

oxidant action viz. magnitude of Piper cubeba capabilities to search free radicals, DPPH,

hydroxyl radical (HO) and superoxide anion radical in different type of systems.[48]

Antimicrobial effect

The essential oil of Piper cubeba showed anti bacterial activity against B. subtilis, Vib.

cholere, C. diphtheria, Sal. typhi, Strep. pyogenes, B. pumilus and Ps. solanacearum. Being

most active against Ps. solanacearum. A combination of piper cubeba with Litsea glutinosa,

of the various combinations was found to be the most active. The essential oil of Piper

cubeba also showed anti bacterial effect against B. subtilis, Esch. coli, Staph. aureus, Sal.

typhi, Sal. paratyphi and pestalotia sp. but not against Sh. niger. The activities of the crude

ethanol extract from Piper cubeba seeds, (-)- cubebin and its semi-synthetic derivatives were

evaluated against oral pathogens. The crude ethanol extract was more active against

Streptococcus salivarius (MIC value of 80μg/mL). (-)-Cubebin displayed MIC values

ranging from 0.20 mm for Streptococcus mitis to 0.35 mm for Enterococcus faecalis. The

natural product (-)-cubebin and its semi-synthetic derivative (-)-hinokinin displayed

bacteriostatic activity at all evaluated concentrations, as well as fungicidal activity against

Candida albicans at 0.28 mm. The O-benzyl cubebin derivative showed fungistatic and

fungicidal effects against C. albicans at 0.28 mm and 0.35 mm, respectively. Also, the other

dibenzylbutyrolactone derivatives [(-)-6,6 –dinitrohinokinin and (-)-O-

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(N,Ndimethylaminoethyl)- cubebin] displayed bacteriostatic and fungistatic effects at the

evaluated concentrations. Moreover, the semi-synthetic derivative (-)-6, 6 - dinitrohinokinin

was the most active compound against all the evaluated micro organisms. Therefore, it may

be suggested that the presence of the carbonyl group at C-9 plus the introduction of polar

groups in the aromatic rings improve the antimicrobial activity of dibenzylbutyrolactone

compounds.[49]

The oils and oil combinations (1:1) were screened against fifteen pathogenic and non-

pathogenic bacteriae. The essential oil of laciniata showed maximum activity against C.

diphtheriae, V. cholerae, B. subtilis and S. aureus and Piper cubeba against S. faecalis, B.

pumilus and P. solanacearum. The combinations of L. chinensis with P. cubeba and C.

asiatica displayed the maximum inhibitory response and the rest failed to show any

synergistic or potentiating effect.[50]

Twenty eight extracts prepared from the fruits of four species, viz. Piper cubeba, P.

retrofractum Vahl syn. P. chaba Hunter non Blume, P. longum and P. nigrum, were

evaluated against bacterial pathogens, such as Staphylococcus albus, Salmonella typhi,

Pseudomonas aeruginosa, Escherichia coli and Bacillus megaterium and one fungus,

Aspergillus niger. Compared to Streptomycin all the extracts exhibited a good antibacterial

activity. Some of the extracts showed antifungal activity as well.[51]

Anthelmintic effect

The oil of the Piper cubeba also showed significant antifungal activity against Aspergillus

flavus, A. fumigatus. Trichodermavird. Curvulari alunata, Alternariatenuis penicillium

funiclosum, P. javanicum, P. striatum and Fusarium solani. The essential oil from fruits

revealed anthelmintic activity against earthworm and tapeworm in vitro. Anti-inflammatory

activities of Piper cubeba (fruit), Physalis angulata (flower) and Rosa hybrida (flower)

clearly exhibited inhibitory effects against acute and subacute inflammation by oral

administration (200 mg/kg) and it also showed significant inhibition of type IV allergic

reaction in mice.[52]

Antileishmanial Activity

The n-hexane, ethyl acetate, methanol, and acetone extracts of Piper cubeba and P.

retrofractum, Vahl. (Piperaceae) were evaluated in vitro against promastigotes of Leishmania

donovani, and all exhibited significant in vitro activity at 100 μg/ml. Two lignans, cubebin

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and hinokinin, were isolated from the hexane extract of P. cubeba; and one bis-epoxy lignan,

(−)-sesamin, and two amides, pellitorine and piplartine, were isolated from the hexane and

methanol extracts of P. retrofractum. Cubebin and piplartine showed significant anti-

leishmanial activity in vitro at 100 μM and were further tested in vivo in a hamster model of

visceral leishmaniasis. Piplartine showed activity at 30 mg/kg dose. This is the first report of

antileishmanial activity of these two plants and their isolated constituents.[53]

Hepatoprotective activity

Methanol and water extract of P. cubeba berries have been shown to display an inhibitory

effect against the hepatitis C virus.[54]

Piper cubeba ethanolic extract has been found effective

in prevention of CCl4-induced hepatic damage in rats. Findings demonstrated that the

treatment with PCEE significantly and dose dependently prevented drug induced increase in

serum levels of hepatic enzymes. Furthermore Piper cubeba ethanolic extract significantly

reduced the lipid peroxidation in the liver tissue and restored activities of defense antioxidant

enzymes NP-SHandCAT towards normal levels. The hepatoprotective effect of PCEE is

attributed to downregulation of proinflammatory cytokines, for example, TNF-𝛼 and IL-6

mRNA expression as well as mRNA expression of iNOS and HO-1 gene, and upregulation of

the IL-10. Histopathological studies have also shown that the PCEE and silymarin could

prevent CCl4-induced hepatic damage in the liver.[55]

The fruits of the Piper cubeba plant

were studied for antioxidant and hepatoprotective activity. The antioxidant potential of the

ethanol extract was examined using a 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical

scavenging activity, reducing power, hydroxyl radical scavenging activity, nitric oxide

radical scavenging activity and hydrogen peroxide radical scavenging activity. The extract

had significant dose-dependent antioxidant activity in all in vitro experiments.

Hepatoprotective activity of the extract was evaluated in rat model of carbon tetrachloride

(CCl4) induced liver damage. CCl4 significantly altered serum marker enzymes and total

protein. The ethanol extract of Piper cubeba attenuated CCl4 induced serum marker enzymes

and total protein. Histology of liver sections of the animals treated with the extracts showed

the presence of normal hepatic cords, absence of necrosis and fatty infiltration which further

evidence the hepatoprotective activity.[56]

In this study extracts of Piper cubeba fruit were

prepared using mechanical method. These extracts include alcoholic, acetonic, chloroformic

and water extract. The chemical composition of each extracts were analyzed also. After that

the antibacterial activity of these extracts were tested against gram negative (G-) Escherichia

coli, Pseudomonas aeruginosa and gram positive (G+) Staphylococcus aureus. All extracts

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show antibacterial activity on these bacteria, but ethanol and acetone extracts were show the

best antibacterial activity S. aureus, followed by chloroform extract and then water extract,

on the other hand water extract showed inhibition activity against E.coli and P. aeruginosae

followed by ethanol, acetone and chloroform extract.[57]

Anti inflammatory, Analgesic and Antiarthritic activity

Anti inflammatory, anti oxidant, anti-allergic and analgesic activities of Piper cubeba has

been studied using chemically-induced edema and arthritis in vivo.[52]

Hinokinin has been

reported to have anti-inflammatory and analgesic effect. Because of the structural

relationship, hinokinin can be synthesized using cubebin as precursor.[44]

Cubebin has been

shown to possess anti-inflamatory, analgesic and trypanocidal activities.[58]

Anticancerous activity

Yatein is also an interesting lignan due to its biological activity and its function as a

biosynthetic precursor of deoxypodophyllotoxin and podophyllotoxin that are well known for

their anticancer properties. It was found that P9605 significantly inhibited growth induced by

beta-estradiol in MCF-7, a human breast cancer cell line. It inhibited aromatase activity,

which is responsible for transforming androgens into estrogens. Competitive binding assays

also indicated P9605 binding to both human apoptosis. This anti growth effect was less

pronounced in androgen-independent PC-3 prostate cancer cell lines. P9605 potently

inhibited 5 alpha-reductase II activity, which is responsible for converting testosterone to its

active form, dihydrotestosterone (DHT), in the prostate. It also acted as an antagonist at

recombinant wild-type androgen receptors (AR). P9605 suppressed cell growth and prostate-

specific antigen (PSA) secretion stimulated by physiological concentrations of DHT in

LNCaP cells. Interestingly, it down-regulated AR levels. In conclusion, the findings suggest

that P9605 may potentially retard the growth of androgen-dependent PC via several

mechanisms.[59,60]

Diuretic and nephroprotective activity

The curative and protective effect of Piper cubeba was studied in gentamicin and cisplatin

induced nephrotoxicity in albino rats. The experimental study demonstrated a significant

protective as well as curative effect of Piper cubeba in both the histological and biochemical

parameter.[61,62]

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CONCLUSION

Kabab Chini (Piper cubeba) is commonly used in different traditional medicine viz

Ayurveda, Unani and Chinese medicine for various disorders and equally acclaimed by

Unani physicians for successful treatment of urogenital disorder and other ailments. Some

experimental researches in recent years also demonstrated its bacteriostatic, anti-viral and ant

cancerous effect. In view of above a comprehensive series of clinical trial should be carried

out to develop it as a drug to combat the different disorders as acclaimed by traditional

medicine.

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