Used in

Unan; S,S'•• 01"

I.I- -lul"n

Shakir Jamil*, Shoaib Ahmad**, Jamal Akhtar and Khursheed Alam

Dept. of Moalijat, Facultyof Unani Medicine, lamia Hamdard, New Delhi-l10062, India

* Correspondent author, E-mail: shoaibpharm@rediffmail.com

**1437, Sector 39 - B, Chandigarh-160036, India

Introduction

Diseases caused by protozoa are

responsible for a considerable morbidity

and mortality,especially in the developing

world. Amoebic dysentery or amoebiasis

is one of such protozoal diseases. It is

caused by Entamoeba histolytica. If

untreated, it may give rise to serious

complications including liver abscesses.

There are some 42 million cases annuallyand an estimated 75,000 deaths across the

world due to this disease. In allopathic

systemofmedicine the disease is generallytreated with metronidazole, although this

drug is poorly tolerated by some patients.

There are a number of antiamoebic drugsherbal origin mentioned in the classical

texts in Unani System of Medicine

(Table 1). Some of these drugs havebeneficial effects in treating the disease inthe experimental animals (Table 2) andhumans in the clinical situations

(Table 3). Both in vivo and in vitro

methods have been developed to assay the

antiamoebic activity of the herbal drugs(single botanicals as well as multi­component formulations).

In in vivo antiamoebic assays

rats are used for determination of activity

against intestinal infectionswhile hamsters

are used for evaluating activity against

hepatic infections. E. histolytica isintroduced into the caecum via rectum

and the. intestine is examined for the

presence of amoebae and ulceration. Liver

infections are initiated by injection ofamoebae into the 10bes.However,in vivo

tests are difficult to perform, time­consuming and are unpleasant for theanimals.

For in vitro antiamoebic assaysthe development of axenic cultures of

Entamoeba histolytica has enabled the

development of in vitro assays.Before the

development of axenic media, it was only

possible to grow the amoebae in presenceof bacteria (polyxenic culture) and it

made interpretation of the results

extremely difficult. Now-a-days, E.histolytica is grown in 96-well

microculture plates in the presence of

serial dilution of herbal drug extracts orisolated compounds. Atthe end of the test

time, the growth of amoebae may beevaluated by visual observation with a

microscope. Alternatively,a colorimetricmethod may be used which involves the

removal of culture medium thus, leavinghealthy amoebae attached to the bottom

of wells while the dead amoebae are

washed away. A measure of the number

of amoebae remaining in the well is

obtained by fixing and staining the

parasites. The quantity of stain taken up isproportional to the number of amoebae

and can be determined byspectrophotometric method.

A relatively simpler method i.e.,

micro dilution technique for the

assessment of in vitro activity againstEntamoeba histolytica has been

developed and validated withmetronidazole. This test has been used to

detect the antiamoebic activitiesofextracts

of Brucea javanica (Linn.) Merrillfruits and Quassia amara Linn. stems.

The activity was found to be associated

with quassinoid-containing fractions. The

50% inhibitory concentrations for somequassinoids against amoebae were

determined by using this microdilution

method. These concentrations rangedfrom 0.019 j.lglmlfor bruceantin, the most

active quassinoid, to greater than 5 j.lgl

ml for glaucarubol, the least active

compound tested. The micro dilution

technique, being more accurate and

precise will be quite useful in searchingthe novel antiamoebic drugs.

Natural Product Radiance Vol 2(1) January-February 2003

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Table 1: Antiamoebic Drugs in Unani System of Medicine

Botanical name

Acacia arabica

Acacia catechu

Aegle marmelosAlstonia scholaris

Balanites aegyptiacaBauhinia racemosa

Boswellia glabraCalotropis proceraCannabis sativa

Cassia fistulaCinnamomum camphoraCinnamomum zeylanicumCochlospermum gossypiumCordia latifoliaCydonia oblongaEmblica officinalisFicus bengalensisFicus carica

Ficus glome rataHelicteres isora

Holarrhena antidysenterica

Hyoscyamus nigerMalva rotundifoliaMalva sylvestrisMangifera indicaMentha arvensis

Mimosa pudicaMimusops elengiMyrtus communisPapaver somniferumPlantago ovataPlantago majorPunica granatumQuercus infectoriaRosa damascena

Rubia cordifoliaRUinex vasicarius

Syzygium cuminii

Family

Mimosaceae

Mimosaceae

Rutaceae

Apocynaceae

Zygophyllaceae

CaesalpiniaceaeBurseraceae

AsclepiadaceaeCannabinaceae

CaesalpiniaceaeLauraceae

Lauraceae

Cochlospermaceae

BoraginaceaeRosaceae

EuphorbiaceaeMoraceae

Moraceae

Moraceae

Sterculiaceae

Apocynaceae

Solanaceae

Malvaceae

Malvaceae

Anacardiaceae

Lamiaceae

Mimosaceae

Sapotaceae

Myrtaceae

Papaveraceae

Plantaginaceae

PlantaginaceaePunicaceae

FagaceaeRosaceae

Rubiaceae

polygonaceae

Myrtaceae

UnaniName

Gondkikar

Kattha

BelgiriSatoona

HingotKachnar

Lohban

PostAkh

BhangAmaltas

Kafoor

Da1chini

Katira

SapistanBihi

Amla

Bargad

Roghan anjeerGular

Maror phaliKurchi

Ajwain khurasaniKhubbazi

Resha khutmi

Khasta-e-Amba

Podina

LajwantiSamar mulsari

Habbulas

Post Khaskhas

Isapghol

BartangPostAnar

Mazu

GuIqand

MajeethChuka

Jamun

Natural Product Radiance Vol 2(1) January-February 2003 '" .1'. 11

Table 2: Pharmacologically proven antiamoebic Unani Drugs

Botanical name Family Unani name Part used

---------.-------------.-- ..----_-!_.----.-.-.-.--.------Aconitum heterophyllum

Aegle marmelos

Ailanthus glandulosa

Allium sativum

Alstonia angustifolia

Artemisia absinthium

Calotropis procera

Cassia fistula

Cinchona ledgeriana

Commiphora wightii

Cyperus scariosus

Euphorbia hirta

Gossypium herbaceum

Holarrhena antidysenterica

Helicteres isora

Momordica dioica

Myristica fragrans

Piper longum

Pistacia intergerrima

Plantago major

Psidium guajava

Punica granatum

Tabernaemontana spp.

Tylophora indica

Ranunculaceae

Rutaceae

Meliaceae

Liliaceae

Apocynaceae

Asteraceae

Asclepiadaceae

Caesalpiniaceae

Rubiaceae

Burseraceae

Cyperaceae

Euphorbiaceae

Malvaceae

Apocynaceae

Sterculiaceae

Cucurbitaceae

Myristicaceae

Piperaceae

Anacardiaceae

Plantaginaceae

Myrtaceae

Punicaceae

Apocynaceae

Asclepiadaceae

Atis Root

Bel

Fruit

Bakayan

Gall

Lehsun

Cloves

Satoona

Root

Afsanteen

Whole plant

Madar

Root, bark

Amaltas

Whole seed

Quinine

Bark

Muqil

Gum resin

Nagarmotha

Fruit

Doodhi kalan

Whole plant

Banola

Seed

Indrajau talkh

Fruit

Marore Phali

Pod

Jungli Karela

Fruit

Jaiphal

Seed

Filfil Draz

Fruit

Kakra singhi

Gall

Bartang

Seed

"Amrood

Fruit

Rum man

Flower, Rind

Gulchandi

Root

Antamul

Root

Table 3: Clinically proven antiamoebic Unani Drugs

Botanical name FamilyUnani namePart used

---_ •....-._--~._.•._-----_._._._._ .._._. __ ._.-.._""-"'~.•_-'""Artemisia absinthium

AsteraceaeAfsanteenWhole Plant

Calotropis procera

AsclepiadaceaeMadarRoot bark

Helicteres isora

SterculiaceaeMarore PhaliPod

Natural Product Radiance Vol 2(1) January-February 2003

Natural Product Radiance Vol 2(1) January-February 2003

Cephaelis ipecacuanha

Holarrhena antidysenterica

Marketed antiamoebic Unani

preparations

A number of drug houses are

engaged in preparation of Unani

medicines in India. Prominent amongthem are Hamdard Dawakhana (Delhi),

Sadar Dawakhana (Delhi) , Shama

~:::"~-r.",.~ ....."",..... =:.,~-", -",T-",officinale Rose. was tested against

E. histolytica in vitro and in vivo. In

the traditional systemof medicine in India,

the formulation is been prescribed forintestinal disorders. The formulation had

a Minimum Inhibitory Concentration

(MIC) of 1000 ~g1ml as compared with

10 ~g1ml for metronidazole.

~--_1t'Ftllle""",_m?~_-",F' -'"

active against E. histolytica in vitro.Quassinoids possessing an unsaturated A­

ring, a lactone ring and a methylene

oxygen bridge in the C-ring such as inbrusatol, a constituent of Brucea

javanica (Linn. ) Merrill , have very

potent action against E. histolytica.Unfortunately,these compounds also have

very high toxicity to mammalian cells andattempts to improve their selectivity by

making structural changes have not so far

been very fruitful. Again, the antiamoebic

activityis due to the inhibition of proteinsynthesis and as these processes appearto be similar in amoebae and mammalian

cells, it is likely to be quite difficult toimprove selectivity. However, it is of

interest to note that one quassinoid ­

glaucarubinone found in Simaroubaglauca, was formerly used in France for

the treatment of amoebic dysentery.The antiamoebic effectof a crude

drug formulation which comprisedextracts of five well known Unani

medicinal herbs, namely, Boerhaaviadiffusa Linn., Berberis aristata DC.,

Tinospora cordifolia (Willd.) Miersex Hook. f. & Thoms., Terminalia

chebula Retz. and Zingiber

Antiamoebic compounds fromUnani Drugs

Although a large number of

natural products have been shown to be

able to inhibit the growth of amoebae, very

fewhave been shown to be selectivelytoxic

to the parasite.

Berberine, a benzylisoquinolinealkaloid common in members of the

Menispermaceae, has been clinicallyusedin the treatment of leishmeniasis.

Berberine has been reported to be

effectiveagainst E. histolytica in vitro.The plant flavonoids{ (-) -epicatechin,

(- ) -epigallocatechin and kaempferol}

have been found to higWyactive againstamoebae.

Conessine is one of the steroidal

alkaloids from the bark ofHolarrhena

antidysenterica (Linn.) Wall. and has

also shown an in vitro activityagainst E.histolytica. Emetine from Cephaelisipecacuanha (Brot.) A. Rich.(Rubiaceae) has been found to be higWyactive in the treatment of both hepatic andintestinal amoebiasis but has some toxic

effects especially on the heart. It inhibits

protein synthesis which is probably

responsible for its antiamoebic action andthe toxic effects seen in man. Several

alkaloids from Strychnos spp. have alsobeen found to be active against amoebae

but in contrast to emetine, they were lesstoxic to cells. Usambarensine,

usambarine, and 18,19­

dihydrousambarine from Strychnosusambarensis have been found to be

higWy active against E. histolytica invitro. Nb-Methylusambarensine was

comparatively less activeagainst amoebae

than was usambarensine. Gossypol, a

polyphenol from cotton seed oil, is also

Conclusion

rate of efficacy in terms of clinical 4.

improvement.

Casinovi C.G., Fardella G. andGandolini G. (1981). PharmEducation & Science, 36(2),116-22.

Chopra R.N.,Chopra I. C.,Handa KL.

and KapurL.D.,Indigenous Systemof Medicine, U.N. Dhur and Sons

Pvt. Ltd., Calcutta, 1958, 2nd edn,

522,603.

Evans W.C., Trease and Evans'

Pharmacognosy, W. B. Saunders &

Company, London, 2002, 15th edn,407-413.

Anturlikar S.D., Gopumadhavan S.,

Mitra S.K., Chauhan, B. 1. and

Kulkarni, R. D., Indian Drugs,

1993,30(11),582-85.

11. Ghosal S., Prasad B.N. and Lakshmi

v., 1Ethnopharmacology, 1996,50,167-70.

12. Jain P.K,VermaR., KumarN.andAnil

Kumar,1Res Ayurveda & Siddha,1985,6 (1,3,4),88-91.

13. Jamil S., Alam K, Ahmad S., AkhtarS. and All A., 1Sci Pharm, 2002,3(3),99-101.

14. Kuhnt M., Probstle A., Bauer R. and

Heinrich M.,Planta Medica, 1993,59 (Suppl), A-665.

Galvez]., Zarzuelo A., Crespo M.E.,Lorente M. D., Ocete M. A. and

Jimenez]., Planta Medica, 1993,59,333-336.

10. Ghosh T.K, Sen T.,Das A.,DuttaA. S.

and Nag A. K. Chaudhuri,

Phytotherapy Res, 1993, 7(6),431- 33.

5. Bhutani K.K.,Sharma G.L.and AllM.,Planta Medica, 1987, 53(6),

532-36.

Ansari A.A.,Rafiquddin M. and Aziz

A.,AClinical Studyof Post-e-Bekh,Madar & Marore phali in ZaheerAmoebai. In Dandia P.C. and S.B.

Vohora (ed) Research &Development of IndigenousDrugs, 1989,322-26.

2. Anonymous, Rog Aur Chikitsa,Hamdard Dawakhana (Wakf), Delhi,

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1. Abdul Wahid and Siddiqui H.H., A

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References

Natural products will continue to

provide novel compounds which may

ultimately lead to new antiamoebic drugs. 6It is important to evaluate locally used .

traditional systems of medicines to

determine their efficacy and safety inclinical situations. There are a number of

drugs of plant-origin in Unani system of 7.

Medicine which have not yet been tried

clinically.It is suggested that after reievent

pharmacognostical and phytochemical

studies (if not done previously), they may

be tried in the experimental models in 8.

animals and human subjects. So, that the

patients may benefit from the traditional

wisdom. It is hoped that further research

will provide new medicines not onlyin the 9form of herbal products but also based .

on pure compounds for the treatment ofamoebiasis.

Berberis aristata

Boerhaavia diffusa

Laboratories (Delhi), Dawakhana Ajmal

KhanTibbiyyaCollege(Aligarh),etc.These

drug houses also prepare and market the

antiamoebic Unanidrugs. These marketed

preparations are being used by the Unaniphysicians in India and abroad in theclinical situations. These formulations are

based on one or more of the herbal drugs

(mentioned in the foregoing text and

tables) and include Dawa-e-Siyah 3.Pechish, Habb-e-Pechish, Safoof-e­Muqliyasa, Sharbat-e-Habbul-As,lawarish Tabashir, lawarish Amla,

lawarish. Mastagi, lawarishSafarjali Qabiz, Majoon SangdanaMurg. These formulations have a high

Natural Product Radiance Vol 2(1) January-February 2003

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Polyherbal Un ani formulation,

Zaght-al-Dam Qavi for hypertensionAclinical evaluation of the efficacyof the polyherbal Unani formulation, Zaght-al-Dam Qavi in hyperten­

sion has been done at lamia Hamdard, Hamdard University,NewDelhi. This Unani formulation consists of Tukhm-e-kahu(Lactuca scariola Linn.), Gul-e-Neelofar (Nymphaea alba Linn. ),Asrol (Rauwolfia serpentina Linn.) andKishneez (Coriandrum sativum Linn.). One dose offormulation containing 109 Kishneez, Tukhm-E-Kahu,lOg,

Gul-e-Neelofar, 5 g and Asrol (root) 19was given orally twice a day for the period of 2 months. The formulation wasfound to be effective in the reduction of clinical symptomps of hypertension in the patients i.e., headache, palpitation,

dizziness, fatigue, nervousness, insomania, etc. The blood pressure was normalized after two months of the treatment

[Siddiqui etal, J Sci Pharmacy, 2002, 3(4),154-157].

Natural Product Radiance Vol 2(1) January-February 2003