Antiamoebic Plants used in Unani System of Medicine

Used in

Unan; S,S'•• 01 "

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Shakir Jamil*, Shoaib Ahmad**, Jamal Akhtar and Khursheed Alam Dept. of Moalijat, Faculty of 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 byEntamoeba histolytica. If untreated, it may give rise to serious complications including liver abscesses.

There are some 42 million cases annually and an estimated 75,000 deaths across the world due to this disease. In allopathic system ofmedicine the disease is generally treated with metronidazole, although this drug is poorly tolerated by some patients.

There are a number of antiamoebic drugs herbal origin mentioned in the classical texts in Unani System of Medicine (Table 1). Some of these drugs have beneficial effects in treating the disease in the experimental animals (Table 2) and humans 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 multi- component 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 is introduced into the caecum via rectum and the. intestine is examined for the presence of amoebae and ulceration. Liver infections are initiated by injection of amoebae into the 10bes.However,in vivo tests are difficult to perform, time- consuming and are unpleasant for the animals.

Forin vitroantiamoebic assays the development of axenic cultures of Entamoeba histolytica has enabled the development ofin vitroassays. Before the development of axenic media, it was only possible to grow the amoebae in presence of 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 or isolated compounds. Atthe end of the test time, the growth of amoebae may be evaluated by visual observation with a microscope. Alternatively,a colorimetric method may be used which involves the removal of culture medium thus, leaving healthy 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 is proportional to the number of amoebae

and can be determined by

spectrophotometric method.

A relatively simpler method i.e., micro dilution technique for the assessment of in vitro activity against Entamoeba histolytica has been developed and validated with metronidazole. This test has been used to detect the antiamoebic activitiesofextracts of Brucea javanica (Linn.) Merrill fruits andQuassia amara Linn. stems.

The activity was found to be associated with quassinoid-containing fractions. The 50% inhibitory concentrations for some quassinoids against amoebae were determined by using this microdilution method. These concentrations ranged from 0.019 j.lglmlfor bruceantin, the most active quassinoid, to greater than 5j.lgl

ml for glaucarubol, the least active compound tested. The micro dilution technique, being more accurate and precise will be quite useful in searching the novel antiamoebic drugs.

Natural Product Radiance Vol2(1)January-February 2003

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Table 1: Antiamoebic Drugs in Unani System of Medicine Botanical name

Acacia arabica Acacia catechu Aegle marmelos Alstonia scholaris Balanites aegyptiaca Bauhinia racemosa Boswellia glabra Calotropis procera Cannabis sativa Cassia fistula

Cinnamomum camphora Cinnamomum zeylanicum Cochlospermum gossypium Cordia latifolia

Cydonia oblonga Emblica officinalis Ficus bengalensis Ficus carica Ficus glome rata Helicteres isora

Holarrhena antidysenterica Hyoscyamus niger

Malva rotundifolia Malva sylvestris Mangifera indica Mentha arvensis Mimosa pudica Mimusops elengi Myrtus communis Papaver somniferum Plantago ovata Plantago major Punica granatum Quercus infectoria Rosa damascena Rubia cordifolia RUinex vasicarius Syzygium cuminii

Family

Mimosaceae Mimosaceae Rutaceae Apocynaceae Zygophyllaceae Caesalpiniaceae Burseraceae Asclepiadaceae Cannabinaceae Caesalpiniaceae Lauraceae Lauraceae Cochlospermaceae Boraginaceae Rosaceae Euphorbiaceae Moraceae Moraceae Moraceae Sterculiaceae Apocynaceae Solanaceae Malvaceae Malvaceae Anacardiaceae Lamiaceae Mimosaceae Sapotaceae Myrtaceae Papaveraceae Plantaginaceae Plantaginaceae Punicaceae Fagaceae Rosaceae Rubiaceae polygonaceae Myrtaceae

UnaniName

Gondkikar Kattha Belgiri Satoona Hingot Kachnar Lohban PostAkh Bhang Amaltas Kafoor Da1chini Katira Sapistan Bihi Amla Bargad Roghan anjeer Gular

Maror phali Kurchi

Ajwain khurasani Khubbazi Resha khutmi Khasta-e-Amba Podina Lajwanti Samar mulsari Habbulas Post Khaskhas Isapghol Bartang PostAnar Mazu GuIqand Majeeth Chuka Jamun

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:

Botanical name Part usedUnani nameFamily

---_

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Asteraceae Afsanteen

Whole Plant

Calotropis procera

Asclepiadaceae Madar

Root bark

Helicteres isora

Sterculiaceae Marore Phali Pod

Natural Product Radiance Vol2(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 among them are Hamdard Dawakhana (Delhi), Sadar Dawakhana (Delhi) , Shama

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officinale ^Rose. was tested against E. histolytica in vitro andin vivo. In the traditional systemof medicine in India, the formulation is been prescribed for intestinal disorders. The formulation had a Minimum Inhibitory Concentration

(MIC) of 1000 ~g1ml as compared with 10 ~g1ml for metronidazole.

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active againstE. histolytica in vitro.

Quassinoids possessing an unsaturated A- ring, a lactone ring and a methylene oxygen bridge in the C-ring such as in brusatol, 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 and attempts to improve their selectivity by making structural changes have not so far been very fruitful. Again, the antiamoebic activityis due to the inhibition of protein synthesis and as these processes appear to be similar in amoebae and mammalian cells, it is likely to be quite difficult to improve selectivity. However, it is of interest to note that one quassinoid - glaucarubinone found in Simarouba glauca, was formerly used in France for the treatment of amoebic dysentery.

The antiamoebic effectof a crude drug formulation which comprised extracts of five well known Unani medicinal herbs, namely,Boerhaavia diffusa Linn., Berberis aristata DC.,

Tinospora cordifolia (Willd.) Miers ex Hook.

f.

Antiamoebic compounds from Unani 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 benzylisoquinoline alkaloid common in members of the Menispermaceae, has been clinicallyused in the treatment of leishmeniasis.

Berberine has been reported to be effectiveagainstE. histolytica in vitro.

The plant flavonoids{ (-) -epicatechin, (- ) -epigallocatechin and kaempferol}

have been found to higWyactive against amoebae.

Conessine is one of the steroidal alkaloids from the bark ofHolarrhena antidysenterica (Linn.) Wall. and has also shown an in vitro activityagainstE.

histolytica. Emetine from Cephaelis ipecacuanha (Brot.) A. Rich.

(Rubiaceae) has been found to be higWy active in the treatment of both hepatic and intestinal amoebiasis but has some toxic effects especially on the heart. It inhibits protein synthesis which is probably responsible for its antiamoebic action and the toxic effects seen in man. Several alkaloids fromStrychnos spp. have also been found to be active against amoebae but in contrast to emetine, they were less toxic to cells. Usambarensine,

usambarine, and 18,19-

dihydrousambarine from Strychnos usambarensis have been found to be higWy active against E. histolytica in vitro. Nb-Methylusambarensine was comparatively less active against amoebae than was usambarensine. Gossypol, a

Conclusion

rate of efficacy in terms of clinical 4.

improvement.

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1

50,167-70.

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1

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References

Natural products will continue to provide novel compounds which may ultimately lead to new antiamoebic drugs. 6 It is important to evaluate locally used . traditional systems of medicines to determine their efficacy and safety in clinical 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 rei event 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 only in the 9 form of herbal products but also based . on pure compounds for the treatment of amoebiasis.

Berberis aristata

Boerhaavia diffusa

Laboratories (Delhi), Dawakhana Ajmal KhanTibbiyyaCollege (Aligarh), etc. These drug houses also prepare and market the antiamoebic Unani drugs. These marketed preparations are being used by the Unani physicians in India and abroad in the clinical 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-e- Muqliyasa, Sharbat-e-Habbul-As, lawarish Tabashir, lawarish Amla, lawarish. Mastagi, lawarish Safarjali Qabiz, Majoon Sangdana Murg. These formulations have a high

Natural Product Radiance Vol2(1)January-February 2003

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38.

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(M. D. Thesis) Department of 15. Misra D.N. and Chaturvedi C., Mehtas J Sci Res, 1980,2(1 &2), 4-11.

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188-90.

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Polyherbal Un ani formulation, Zaght-al-Dam Qavi for hypertension

A clinical 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 ofTukhm-e-kahu

(Lactuca scariola Linn.), Gul-e-Neelofar (Nymphaea alba Linn.),Asrol (Rauwolfia serpentina Linn.) and Kishneez (Coriandrum sativum Linn.). One dose offormulation containing 109Kishneez, Tukhm-E-Kahu,lOg, Gul-e-Neelofar, 5 g andAsrol(root) 19 was given orally twice a day for the period of 2 months. The formulation was found 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,