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ANTIDIARRHOEAL MEDICINAL PLANTS 717

Copyright © 2006 John Wiley & Sons, Ltd. Phytother. Res . 20, 717–724 (2006)DOI: 10.1002/ptr

Copyright © 2006 John Wiley & Sons, Ltd.

PHYTOTHERAPY RESEARCHPhytother. Res. 20, 717–724 (2006)Published online 18 April 2006 in Wiley InterScience(www.interscience.wiley.com) DOI : 10.1002/ptr.1907

REVIEW ARTICLE

Phytochemicals from Traditional MedicinalPlants used in the Treatment of Diarrhoea:

Modes of Action and Effects on IntestinalFunction

Enzo A. Palombo*Environment and Biotechnology Centre, Faculty of Life and Social Sciences, Swinburne University of Technology, HawthornVictoria 3122, Australia

Medicinal plants have been used as traditional treatments for numerous human diseases for thousands of years. Diarrhoeal diseases continue to be a major cause of morbidity and mortality throughout the world and

there is renewed interest in the discovery of novel compounds that can be used to ght these diseases.Numerous studies have validated the traditional use of antidiarrhoeal medicinal plants by investigating thebiological activity of extracts of such plants, which have antispasmodic effects, delay intestinal transit, suppressgut motility, stimulate water adsorption or reduce electrolyte secretion. Of the numerous phytochemicals(such as alkaloids, tannins, avonoids and terpenes) present in active extracts, tannins and avonoids arethought to be responsible for antidiarrhoeal activity by increasing colonic water and electrolyte reabsorption.Others act by inhibiting intestinal motility. As some of the active ingredients are potentially toxic, there is aneed to evaluate the safety of plant preparations. A few clinical trials have evaluated the safety and tolerabilityof traditional and herbal medicine preparations used to treat diarrhoea and generally indicate that minimalside effects are observed. However, with the increased popularity of plant-derived and herbal medicines inWestern society, the benets and potential dangers of these medicines must be considered. Copyright © 2006John Wiley & Sons, Ltd.

Keywords: diarrhoea; medicinal plants; phytochemicals; alkaloids; avonoids; phenolics; tannins.

Received 29 January 2006 Accepted 2 March 2006

* Correspondence to: Dr Enzo A. Palombo, Faculty of Life and SocialSciences, Swinburne University of Technology, P.O. Box 218, HawthornVIC, 3122, Australia.E-mail: [email protected]/grant sponsor: Sunshine Foundation.Contract/grant sponsor: Swinburne University Alumni & DevelopmentOfce.

other viral (adenovirus, enterovirus and norovirus),bacterial ( Escherichia coli , Salmonella , Shigella ,Campylobacter and Vibrio cholerae ) and parasitic(Cryptosporidium and Giardia ) agents are importantpathogens (Allen et al. , 2003). Oral rehydration therapy(ORT) remains the major treatment for diarrhoea,although it does not reduce the volume or durationof diarrhoea (Subbotina et al. , 2003). Other treatmentoptions include antibiotics and gut motility suppressingagents, which aim to reverse dehydration, shorten thelength of illness and reduce the period of time an indi-vidual is infectious (Allen et al. , 2003). Treatment with

pharmacological agents that are pathogen-specic orthat suppress severe symptoms would be of benet topatients suffering from prolonged diarrhoea (Takahashiet al. , 2001; Oi et al. , 2002).

Traditional plant-based medicines. Medicinal plantshave been used as traditional treatments for numeroushuman diseases for thousands of years and in manyparts of the world. In rural areas of developing coun-tries, they continue to be used as the primary source of medicine (Chitme et al. , 2003). About 80% of peoplein developing countries use traditional medicines fortheir health care (Kim, 2005). The natural productsderived from medicinal plants have proven to be an

abundant source of biologically active compounds, manyof which have been the basis for the development of new lead chemicals for pharmaceuticals. With respect

INTRODUCTION

Diarrhoeal diseases. Despite advances in the under-standing of the causes, treatment and prevention of diarrhoeal diseases, an estimated 4.6 million people,including 2.5 million children, die from diarrhoea everyyear (Kosek et al. , 2003; Thapar and Sanderson, 2004),particularly in developing countries. The World HealthOrganization denes diarrhoea as three or more looseor watery stools in a period of 24 h (Allen et al. , 2003),although changes in the consistency of stools are im-

portant indicators of disease. Diarrhoea can be classi-ed as acute or chronic, with acute diarrhoea being themost common form. Acute diarrhoea has an abruptonset, resolves within about 14 days and is usuallycaused by an infectious agent, although drugs, poisons(including bacterial toxins) or acute inammatory reac-tions can contribute (Thapar and Sanderson, 2004).Worldwide, rotavirus is the major cause of infectiousdiarrhoea, particularly among young children, however,




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to infectious diseases, the increasing resistance in manycommon pathogens to currently used therapeutic agents,such as antibiotics and antivirals, has led to renewedinterest in the discovery of novel antiinfective com-pounds. As there are approximately 500 000 plantspecies occurring worldwide, of which only 1% hasbeen phytochemically investigated, there is great poten-tial for discovering novel bioactive compounds. How-ever, according to the United Nations EnvironmentProgramme World Conservation Monitoring Centre,current extinction rates of plants and animals mean thatthe world is losing one major drug every 2 years(Groombridge and Jenkins, 2002).

There have been numerous reports of the use of tra-ditional plants for the treatment of diarrhoeal diseases.Many plant-derived medicines used in traditional Afri-can, American, Asian, European and other indigenousmedicinal systems have been recorded in pharmacopeiasas agents used to treat diarrhoea. The purpose of thisreview is to present some recent examples of studiesthat have served to validate the traditional use of medicinal plants with specic biological activity. Inparticular, traditional medicinal plant extracts orphytochemicals that have been shown to reduce thesymptoms of diarrhoea will be discussed. In addition,studies that have investigated the mode of antidiarrhoealaction and the safety of plant-derived medicines will bedescribed. The antimicrobial activities of medicinalplants and plant products have been reviewed previ-ously (Cowan, 1999; Kalemba and Kunicka, 2003) andwill not be discussed here.

EVALUATING THE ANTIDIARRHOEALACTIVITY OF MEDICINAL PLANTS

Many animal-based studies have investigated thebioactivity and effects on intestinal function of plants traditionally used as treatments for diarrhoea.Plant extracts can have antispasmodic effects, delaygastrointestinal transit, suppress gut motility, stimulatewater adsorption or reduce electrolyte secretion. Theseactivities may explain the benets of using particularplants in the treatment of diarrhoeal disease. To deter-mine the antidiarrhoeal activity of an extract, diarrhoeais induced by an agent such as castor oil, arachidonicacid, prostaglandin E 2 or magnesium sulphate. Theability of the extract under investigation to confer pro-

tection is then determined by measuring faecal output.As these agents have different mechanisms of action,(for example, castor oil increases peristaltic activity andalters the permeability of the intestinal mucosa towater and electrolytes, while magnesium sulphate is anosmotic active agent), the nature of the antidiarrhoealactivity can be determined (Galvez et al. , 1993; Abgoret al. , 2004). Gastrointestinal transit is usually deter-mined by measuring the transit of a charcoal plug (a5% charcoal suspension in 10% aqueous solution of tragacanth powder administered orally). The distancetravelled by the plug is expressed as a percentage of the total length of the small intestine (Akah et al. , 1999;Abdullahi et al. , 2001; Agbor et al. , 2004). The effect on

gut motility is determined by measuring the ability of an extract to block contractions evoked by agonists (e.g.acetylcholine, histamine and nicotine) (Akah et al. , 1999;

Murugesan et al. , 2000; Abdullahi et al. , 2001). Theability of an extract to stimulate water adsorption orreduce electrolyte secretion is measured using ligatedintestinal loop or colon assays (Oi et al. , 2002; Agboret al. , 2004), where sections of gut are ligated and plantextracts are introduced into the isolated sections. Atthe end of the experimental period, the contents of theligated gut are evaluated by measuring the amount of uid accumulated and the concentration of Na +, K+ andCl− ions. The net absorption of water and electrolyteswith and without extract is determined. For the deter-mination of specic bioactivity, the sections can alsobe treated with an agent known to result in uid accu-mulation and electrolyte secretion into the intestinallumen, such as cholera toxin, to determine if theextract can inhibit the effects of these agents.

TRADITIONAL MEDICINAL PLANTS WITHDEMONSTRATED ANTIDIARRHOEALACTIVITY: PHYTOCHEMICAL ANALYSIS ANDMODES OF ACTION

The plants described below have been validated as treat-ments for diarrhoea on the basis of their ability toprevent or ameliorate diarrhoeal symptoms induced inexperimental animals or, where tested, in clinical trialsin humans. Phytochemical analysis of plant prepara-tions and the identication of active components thereinhave helped to explain the mechanism of antidiarrhoealactivity. Identication of plants with veried activity isthe rst phase in the discovery of lead compounds thatmay be developed into novel therapeutic agents.

Traditional medicinal plants used in India. The roots of Jatropha curcus (Euphorbiaceae) are used traditionallyin the western coastal areas of India to control dysen-tery and diarrhoea (Mujumdar et al. , 2000). Methanolextracts have exhibited dose-dependent inhibition of castor oil-induced diarrhoea and intraluminal uidaccumulation, as well as small intestinal transit. Theextracts may act by inhibiting prostaglandins and reduc-ing small intestinal propulsive movement. In a similarmanner, Chitme et al. (2003) have investigated themedicinal plant Calotropis gigantea (Asclepiadaceae).A water:ethanol (50:50) extract produced a statisticallysignicant reduction in the severity and frequency of diarrhoea produced by castor oil. In addition, both

castor oil-induced intestinal uid accumulation andintestinal volume content were inhibited signicantly.Numerous phytochemicals, including sugars, avonoids,avonol glycosides and terpenes, have been identiedin this plant and these may mediate the antidiarrhoealproperties, although the active component has not beendened. An ethanol extract of the root of Trichodesmaindicum (Boraginaceae), another Indian medicinal plantused to treat diarrhoea, has been found to reducecastor oil-induced enteropooling and the propulsion of a charcoal meal in experimental animals (Perianayagamet al. , 2005). Similarly, a chloroform extract of the rootsof Aegle marmelos (Correa), a medicinal plant used inIndia, Burma and Sri Lanka for a variety of ailments,

including diarrhoea, displayed signicant activity againstcastor oil-induced diarrhoea which was comparable tothe antidiarrhoeal agent, loperamide (Mazumder et al. ,






720 E. A. PALOMBO

Traditional medicinal plants used in Africa. The leavesand stem bark of Alchornea cordifolia (Euphorbiaceae)are used in African folk medicine to treat urinary,respiratory and gastrointestinal disorders (Agbor et al. ,2004). A leaf extract has been shown to ameliorate thesymptoms of castor oil-induced diarrhoea in rats andreduce gastrointestinal transit of a charcoal meal in mice.Measurement of the uid volume and Na +, K+ and Cl −

concentrations in tied-off rat colon indicated that theextract stimulated net water absorption and reducedelectrolyte secretion. Similarly, an extract of the Nige-rian antidiarrhoeal plant Pentaclethra macrophylla(Mimosaceae) signicantly reduced faecal output of castor oil-induced diarrhoea in rats, signicantly reducedgastrointestinal motility in mice and blocked contrac-tions of guinea-pig ileum evoked by various drugs (Akahet al. , 1999). An extract of the roots of Terminalia avi-cennoides (Combretraceae) produced a dose-dependentreduction of spontaneous and acetylcholine-inducedcontraction of rabbit jejunum, reduced gastrointestinaltransit and protected mice against castor oil-induceddiarrhoea (Abdullahi et al. , 2001).

A study by Atta and Mouneir (2004) reported on theantidiarrhoeal properties of six Egyptian medicinalplants. At a dose of 200 mg/kg, some of the plant ex-tracts showed a signicant effect on castor oil-induceddiarrhoea in rats, while the effects were better with anincreased dose of 400 mg/kg. Some of the extracts in-duced a dose-dependent relaxation of rabbit duodenalsmooth muscle while others increased the contractileforce in contractions. Various phytochemicals have beenidentied, including tannins, avonoids, unsaturatedsterols, triterpenes, carbohydrates, lactones, proteins/amino acids and saponins, although the active ingre-dients have not been conrmed. Similarly, severalmedicinal plants used by people in the DemocraticRepublic of Congo (Longanga Otshudi et al. , 2000),Nigeria (Agunu et al. , 2005) and by Zulu traditionalhealers (Lin et al. , 2002) to treat diarrhoea have beenevaluated. These plants showed activity that supportedtheir traditional use, including activity against entericpathogens, and activity in experimental models of diar-rhoea in mice or rats.

A number of plants that have been used as traditionalmedicines in Africa for the treatment of diarrhoeaand dysentery have been recently described in detailby Mueller and Mechler (2005) and are summarizedhere.

• The esh of the fruit of the baobab tree, Adansoniadigitata (Bombacaeae), is eaten raw as a treatmentfor diarrhoea and dysentery. A clinical study inSenegal compared Adansonia fruit with ORT (82children in each group) and found no signicantdifference between the two treatments in terms of duration of diarrhoea and increase in weight, thusconrming the efcacy of the traditional medicine.The astringent constituents of the fruit may explainthe medicinal properties, although the high levelsof tartaric acid can lead to gastrointestinal irritationif large quantities of fruit are consumed.

• Euphorbia hirta (Euphorbiaceae) is used widelyin Western Africa for the treatment of diarrhoea.

The active constituent, quercitrin, is able to reducediarrhoea induced by castor oil and prostaglandinE 2 in mice. Clinical studies have supported the use

of Euphorbia hirta extracts for the treatment of amoebic dysentery, where 83.3% of patients in onestudy and 92.5% in another treated with an ethanolextract of the plant were cured.

• The bark, root or leaves of the mango tree, Mangiferaindica (Anacardiaceae), are macerated or made intodecoctions or teas. The preparations are drunk orused as enemas to treat diarrhoea. The high tannincontent of the leaves and bark may explain therelief provided for the condition due to astringentand antiinammatory effects. However, there are noclinical studies to support this.

• Teas, decoctions or macerations of the leaves of theguava tree, Psidium guajava (Myrtaceae), are wellknown as treatments for diarrhoea in tropical coun-tries. Independent experimental studies in micesupport the use of decoctions of dried leaves andaqueous extracts of leaves to treat diarrhoea, althoughno clinical studies have conrmed these observations.The active component is believed to be quercitrin(Galvez et al. , 1993) (Fig. 2).

• Decoctions or extracts of the leaves of pomegranate,Punica granatum (Punicaceae), are used in manycountries to treat diarrhoea. In the Chinese pharma-copeia, the skins of fruit are recommended. The hightannin and alkaloid content of the skins are possiblyresponsible for the antidiarrhoeal effects. An orallyadministered methanol extract of the seeds, contain-ing steroids, avonoids and tannins, has been shownto reduce signicantly the frequency of stools andreduce gastrointestinal motility in mice. No clinicalstudies are available to support the experimental stud-ies. The alkaloids found in all parts of the plant meanthat high doses of P. granatum are toxic.

• The leaves, roots and seeds of paw paw, Carica papaya (Caricaceae), are used to treat bloody diar-rhoea, although no experimental studies or evidenceof efcacy are available. Similarly, although used inUganda and Congo, there is no experimental or clini-cal evidence for the efcacy of the leaves of thepassion ower, Passiora incarnata (Passioraceae),for the treatment of diarrhoea.

Other traditional medicinal plants and herbs. Blackand long peppers are commonly used as components of

Figure 2. The avonoid ternatin inhibits intestinal transit, secre-tion and motility (Rao et al. , 1997) while quercitrin, anotheravonoid, modulates arachidonic metabolism (Galvez et al. ,1993).






722 E. A. PALOMBO

Phytochemical analysis of a number of medicinal plantscommonly found along the Mediterranean coast andused to treat diarrhoea identied tannins and avonoidsas the likely active antidiarrhoeal constituents as thesewere found in all plants tested (Atta and Mouneir, 2005).Yavada and Jain (2005) have recently identied a newavone glycoside, 5,7,4 ′-trihydroxy-6,3 ′-dimethoxyavone-7- O -α -L-arabinopyranosyl-(1 →6) - O -β -D -galactopyranoside from Melilotus indica (Leguminosae),a medicinal plant used in various applications, includ-ing the treatment of infantile diarrhoea, found in India,the Middle East and Europe. This compound was foundto exhibit antibacterial activity against pathogens thatcaused diarrhoea.

Herbs with astringent properties, such as meadow-sweet, Filipendula ulmaria (Rosaceae), agrimony,

Agrimonia eupatoria (Rosaceae), shepherd’s purse,Capsella bursa-pastoris (Cruciferae) and cranes-bill, Geranium maculatum (Geraniaceae), are recom-mended treatments for diarrhoea and are thought tobe useful as they bind to the mucosal lining of the smallintestine (Hoffman, 1993).

While not a traditional medicine, the high content of avonoids prompted Vitali et al. (2005) to investigatethe antidiarrhoeal properties of an extract from Jaqcuezgrapes, which are commonly used to produce wines.The extract (containing large amounts of proanthocy-anidins with lower amounts of anthocyanidins andhydroxycinnamic acids) was able to signicantly inhibitcastor oil-induced diarrhoea, intestinal uid accumula-tion and gastrointestinal transit. The safety of phytoch-emicals present in these grapes have been proventhrough many years of human consumption, hence theirapplication in this context should not pose a health risk.

As indicated above, phytochemical screening of plantsextracts (made in organic solvents or water) has re-vealed the presence of numerous chemicals includingalkaloids, tannins, avonoids, sterols, terpenes, carbo-hydrates, lactones, proteins, amino acids, glycosides andsaponins (Table 1). Of these, tannins, avonoids,phenolics and alkaloids are thought to be responsiblefor antidiarrhoeal activity. Investigations of the modeof action indicate that tannins and avonoids increasecolonic water and electrolyte reabsorption and otherphytochemicals act by inhibiting intestinal motility.

SAFETY CONSIDERATIONS

Issues about the safety of medicinal plants and herbalsare of concern with all forms of these medicines, notonly those used to treat diarrhoea. This has been high-lighted by recent examples of herbal medicines thathave been linked to serious adverse effects (de Smet,2002; Philip, 2004), including herbal preparationsderived from comfrey which have been used to treatdiarrhoea (Stickel and Seitz, 2000). The use of comfreyleaves has been identied as a health hazard, leadingto hepatic toxicity (veno-occlusive disease) in humans.This toxicity appears to result from the conversionof pyrrolizidine alkaloids into reactive pyrroles oralkaloid-N-oxides by hepatic enzymes. The toxicity

leads to necrosis of hepatocytes and mesenchymal cellsand eventually results in liver damage in the form of portal hypertension.

Some of the active ingredients of medicinal plantsand herbs used in the treatment of diarrhoea arepotentially toxic, although in some cases, chemicalsbesides those that constitute the active ingredients canbe responsible for toxicity. For example, preparationsof the leaves and roots of Maytenus senegalensis (con-fetti tree) are used in various countries of Africa totreat diarrhoea (Mueller and Mechler, 2005). However,the plant is acutely and highly toxic and is not re-commended for any purpose. Instead of the activeantidiarrhoeal component being toxic, some of the toxi-cological effects are due to a constituent found in theleaves, maytansine.

In response to the need to evaluate the safety of plants preparations, a limited number of clinical trialshave investigated the safety and tolerability of herbalmedicine preparations used to treat diarrhoea. Thesehave generally indicated that minimal side effects areobserved. However, with the increased popularity of plant-derived and herbal medicines, particularly inWestern society, the benets and potential dangers of these medicines must be considered.

Safety of commercially available antidiarrhoeal plantmedicines. Plant-derived antidiarrhoeal medicines thatare available commercially include Seirogan (Kuge et al. , 2003), tormentil root (Subbotina et al. , 2003),Zangrado (Miller et al. , 2000) and Kampo (Oi et al. ,2002). Seirogan, which has been used throughout Asiafor more than a century, has been assessed for safety innumerous studies. The active ingredient of this medica-tion is wood creosote, an oily liquid obtained by thefractional distillation of beechwood tar that consists of many simple phenolic compounds (Fig. 5). Oral doses(ve doses of 45–225 mg every 2 h) of wood creosotewere found to be safe and well tolerated with minimalside effects (Kuge et al. , 2003). In addition, doses of up to 200 mg/kg body weight/day did not show evidenceof oncogenicity in rats, further supporting the safety of this product (Kuge et al. , 2001).

Tormentil root, Potentilla tormentilla (Roseaceae) hasbeen used as a folk medicine in many parts of Europefor the treatment of diarrhoea. While several manufac-turers market tormentil root extract and it is consid-ered safe and non-toxic, only a single clinical study hasbeen conducted to test its efcacy in treating diarrhoea(Subbotina et al. , 2003). This study showed thatthe extract was effective in reducing the duration of rotavirus diarrhoea in children admitted to hospital from

5 days in the untreated group to 3 days in the treatedchildren ( p < 0.0001). Stool output was reduced( p < 0.029), stool consistency was normalized earlier( p < 0.0001), less parenteral rehydration was required( p = 0.0009) and length of hospitalization was reduced( p < 0.0001) in treated children compared withcontrols. The study concluded that tormentil root is asafe and effective treatment that reduces uid loss andshortens the length of rotavirus diarrhoea.

Interactions between plant medicines and prescriptiondrugs. As herbal medicines are often used in conjunc-tion with prescription drugs, a relevant health andsafety concern is the potential interaction between

plant extracts and drugs. Given that herbal medicinescontain many active ingredients, the large number of pharmacologically active compounds increases the



ANTIDIARRHOEAL MEDICINAL PLANTS 723


Another important issue is the safe use of herbalmedicines in children. Given that a major target groupof antidiarrhoeal preparations is likely to be youngchildren, and the long-term use of herbal medicines inchildren is not recommended because of the potentialeffect on developing cells and tissue, the safety of such preparations must be fully examined. As childrendiffer from adults in their adsorption, distribution,metabolism and excretion of certain substances, theymay be more vulnerable to the adverse affects of herbalmedicines (Woolf, 2003). A study of the mutagenicpotential of an extract of Stachitarpheta jamaicensis(Verbenaceae), a plant commonly used in Cuba as avermifuge and treatment for diarrhoea, showed no posi-tive responses in an Ames mutagenicity assay, noinduction of micronuclei and an absence of toxicity tobone marrow in mice (Ramos et al. , 2001). While thisstudy indicated that this extract was safe and did notinduce genetic damage, further such studies of plant-derived medicines are needed. In general, the use of plant and herbal therapies is not recommended forchildren (Philip, 2004) or should be used with cautionafter consultation between parents and a clinician,especially if the child is being treated with conventionalmedication (Woolf, 2003).

CONCLUSIONS

Modern scientic evaluation of medicinal plants andherbs is mainly concerned with validating the traditionaluse of plants and identifying the active components of extracts and preparations. While this may be importantin situations where the plant in question also producespotentially toxic compounds, it is possible that a numberof components could act synergistically to produce theobserved therapeutic effects. Hence, separating the in-dividual components may lead to a loss of the desiredactivity. As a result, continued examination of tradi-tional plant medicines is required not only to establishthe scientic basis for activity, but enable the quality,efcacy and safety of such preparations to be betterassessed. In particular, appropriately designed clinicaltrials will provide the necessary evidence to supportthe efcacy of traditional medicines. With respect totraditional medicines used to treat diarrhoeal diseases,such medicines will continue to be used as long as thereare communities with limited access to modern thera-

pies. In the future, it may be possible to augment con-ventional treatments, such as ORT, with plant extractsresulting in complementary treatments leading to areduction in the length of symptoms. The evidenceprovided by recent studies of traditional plant-basedtherapies encourages further investigation in the anti-cipation that alternative treatments for diarrhoealdiseases will be developed.

Acknowledgements

Financial support for the author’s research on medical plants hasbeen generously provided by the Sunshine Foundation and the

Swinburne University Alumni & Development Ofce.

Figure 5. Simple phenolics are some of the major componentsof wood creosote (Kuge et al. , 2003; Morino et al. , 2004; Ogataand Shibata, 2004). 4,5-Dimethylresorcinol has been shown toinhibit Cl − secretion (Ogata and Shibata, 2004).

likelihood of interactions taking place. For example,avonoids exhibit a range of biological activities andhave the ability to modulate several enzymes or cellreceptors, mainly as a result of their antioxidant prop-erties. In contrast, synthetic drugs usually contain sin-gle chemical entities making drug–drug interactions lesslikely (Izzo, 2004). This highlights the need to identifyand possibly purify active components from medicinal

plant preparations as the potential for adverse inter-actions with puried compounds is less likely.A number of phytochemicals, including piperine,

avonoids, triterpenoids, anthraquinones, polyphenolsand alkaloids (some of which are present in anti-diarrhoeal preparations) interact with and inhibitcytochrome P450 systems. This can impact on thepharmacokinetics of any co-administered drugs metabo-lized by these systems (Zhou et al. , 2000). For example,piperine (Fig. 3) has been shown to inhibit arylhydro-carbon hydroxylase and 7-ethoxycourmarin deethylaseby noncompetitive mechanism. Inhibition or induc-tion of specic cytochrome P450 enzymes can lead toadverse drug interactions, including some fatal inter-

actions (Zhou et al. , 2000).




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