Traditional Medicinal Plants Used in the Treatment of Diarrhea that Display Antimicrobial Activity

This section will describe some recent studies that have sought to validate the use of particular plants as traditional treatments for diarrhea. Finding experimental evidence for activity against pathogens known to cause diarrheal disease was the major purpose of such studies, although some have also included phytochemical analysis of plant preparations.

Nigella satavia (Ranunculaceae), commonly known as black seed or black cumin, is used in Europe, Arabian countries, and the Indian subcontinent for culinary and medicinal purposes [22]. It is used to treat numerous ailments, including diarrhea, and its essential oil has been shown to exhibit activity against Staphylococcus aure-us, Salmonella, Shigella, V. cholerae, and E. coli. The major constituents of the essential oil are thymoquinone, p-cymene, carvacrol, t-anethole, 4-terpineol, and longif-oline.

Swertia corymbose (Gentianaceae) is traditionally used in Indican medicine as an antidote for poisoning, diarrhea, and as a stomach wash in cattle [23]. Hexane, chloroform, and methanol extracts show antibacterial activity against a wide range of microorganisms, including a number that cause diarrhea (E. coli, Salmonella, V. cholerae, and Staphylococcus aureus). Alkaloids, flavones, lignins, phenols, proteins, quinine, saponins, starch, steroids, tannins, and triterpenes have been identified in the solvent extracts.

Cocos nucifera (Palmae) is widely distributed on the coast of north-eastern Brazil. The husk fibre decoction is used in the traditional medicine of north-eastern Brazil for treating diarrhea and arthritis [24]. A crude water extract and four out of five fractions of this extract showed selective activity against S. aureus, with catechins and B-type procyanidins thought to be responsible for this activity. Methanol and water extracts of this plant were also found to have significant activity against ente-ropathogens in a recent study of traditional Mexican plants used to treat diarrhea and dysentery [25]. Other Mexican plants with significant antibacterial activity included Caesalpinia pulcherria (Leguminoceae), Geranium mexicanum (Gerania-ceae), Hippocratea excelsa (Hippocrateaceae), and Punica granatum (Puniaceae).

Extracts of guava, Psidiumguajava (Myrtaceae), and paw paw, Caricapapaya (Ca-ricaceae), which are both used in Brazilian traditional medicine, have been tested for their ability to inhibit enterotoxigenic E. coli (ETEC) and S. aureus [26]. While ethanol, acetone, and water extracts of guava were able to inhibit both bacteria, papaya extracts showed no activity. Similarly, extracts of papaya were not found to have significant activity in the study by Alanis et al. [25].

A study of 10 plants used in Indian traditional medicine to treat dysentery and diarrhea showed that some displayed high antibacterial activity, while little activity was detected in others [27]. Those that were highly active included garlic (Allium sativum), svet kanchan (Bauhinia racemosa), tea (Camellia sinensis), garden spurge (Chamaesyce [Euphorbia] hirta), and velvet leaf (Cissampelos pareira). Sweet flag (Acorus calamus), guava (Psidium guajava), and globe thistle (Sphaeranthus indicus) were moderately active, while neem (Azadirachta indica) and sweet indrajao (Wrightia tinctoria) were only weakly active or inactive. Vibrio cholerae was the most susceptible organism, followed by a number of Shigella spp., ETEC, and Klebsiella. It is interesting to note that the study by AlanĂ­s et al. [25] did not find significant antibacterial activity with Allium sativum.

Methanol and water extracts of a number of medicinal plants used to treat dysentery and diarrhea in the Democratic Republic of Congo showed activity against one or more enteropathogens, including Shigella, Salmonella, E. coli, Vibrio, and Campylobacter [28]. The active plants were Roureopsis obliquifolialata (Connara-ceae), Cissus rubiginosa (Vitaceae), and Epinetrum villosum (Menispermaceae) and it was proposed that the antibacterial action might be attributed to the presence of alkaloids in Epinetrum villosum, and tannins and saponins in the other two plants.

Paulo et al. [29] investigated the activity of Cryptolepsis sanguinolenta (Asclepiada-ceae), a shrub indigenous to West Africa, against Campylobacter jejuni, C. coli, and V. cholerae. Although this plant is not used in traditional diarrheal treatment, the authors wished to determine if the medicinal uses of this endemic plant could be extended to include antidiarrheal therapy. Ethanol extracts of the roots and the main phytochemical, cryptolepine (Fig. 12.2), displayed activity against the bacteria that was sometimes greater than antibiotics used to treat infections caused by these pathogens, suggesting that the roots could be useful as an alternative therapy for diarrhea.

Cryptolepine

Piperine

Cryptolepine

Fig. 12.2 Piperine, an alkaloidal constituent of black and long peppers has antidiarrheal activity [30], but is also able to inhibit cytochrome P450 enzymes [31]. Other alkaloids, such as cryptolepine [29] and berberine [32], display antibacterial activity.

Berberine

Diehl et al. [13] evaluated 60 plants collected in the Ivory Coast used traditionally in human or veterinary medicine to treat worm infections (worms in general, round worms, Guinea worms, or flatworms), diarrhea and dysentery or abdominal pain for their antihelminthic activity. Fifty per cent of the selected plants showed activity against eggs of Haemochonus contortus, with 32% showing high activity.

Considering that rotavirus is one of the major diarrheal pathogens, there has been surprisingly little research on the activity of traditional plants against this virus. While ORT remains the main treatment for rotavirus diarrhea and there has been considerable progress in the development of a human rotavirus vaccine, virus-specific therapy will still be required for individuals with persistent diarrhea [5, 15].

An extensive investigation of 100 British Columbian medicinal plant extracts found only one, derived from the roots of Lomatium dissectum (Umbelliferae), which was active against bovine rotavirus [16]. This extract completely inhibited viral cytopathic effects on African green monkey kidney cells, MA104. Clark et al. [14] investigated the ability of crude theaflavins extracted from black tea, Camellia sinensis (Theaceae), to inhibit bovine rotavirus. Theaflavin and gallate derivatives were able to inactivate rotavirus, although the crude extract had greater activity than purified theaflavin or any of the high-performance liquid chromatography (HPLC)-purified fractions. Some of the fractions showed synergism, having greater activity when combined than when tested individually. This study supports the anecdotal data from Egypt and India and Japanese folklore that black tea is a cure for gastroenteritis. Stevia rebaudiana (Asteraceae) originates from Paraguay and has been used as a medicinal plant for a long time [5]. The hot water extract has been shown to display antibacterial activity against E. coli and other food-borne pathogens and is able to inhibit the replication of human rotavirus. The extract is not inactivated by exposure to acid at pH 2, suggesting it may be clinically useful as it can survive passage through the stomach. Anti-rotavirus activity appears to be the result of blocking of virus binding by a specific anionic polysaccharide fraction.

Tormentil root, Potentilla tormentilla (Roseaceae) has been used as a folk medicine in many parts of Europe for the treatment of diarrhea. While several manufacturers market tormentil root extract and it is considered safe and nontoxic, only a single clinical study has been conducted to test its efficacy in treating diarrhea. The study by Subbotina et al. [4] showed that the extract was effective in reducing the duration of rotavirus diarrhea in children admitted to hospital from five days in the untreated group to three days in the treated children (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 with controls. The study concluded that tormentil root is a safe and effective treatment that reduces fluid loss and shortens the length of rotavirus diarrhea.

Recently, 12 medicinal plants used in Brazil to treat diarrhea were evaluated for their ability to inhibit the growth of simian and human rotavirus [15]. Hot water extracts of the seeds of Myristica fragrans (Myristiaceae) were able to inhibit human rotavirus, the leaves of Anacardium occidentale (Anacardiaceae) and Psidium guaja-

va (Myrtaceae) inhibited simian rotavirus, while the bark of Artocarpus integrifolia (Moraceae) and the leaves of Spongias lutea (Anacardiaceae) inhibited both. The level of inhibition considered to be anti-rotaviral was greater than 80%. Of interest was the finding that a number of tested plant extracts were weakly active or ineffective, suggesting that the plants act on pathogens other than rotavirus or that the plants might only be useful against diarrhea caused by pathophysiological disturbances.

Decoctions of the roots and leaves of Helianthemum glomeratum (Cistaceae) are used by the Maya people of southern Mexico to treat diarrheal pain, particularly in cases of bloody diarrhea [11]. Crude extracts and isolated compounds were evaluated for activity against E. histolytica and G. lamblia. Methanol extracts obtained from the aerial parts and roots were active against trophozoites of E. histolytica but not G. lamblia. However, the flavonoids kaempferol and tiliroside present in the aerial parts were active against both protozoa. Polyphenols, found in the aerial parts and roots, were also antiprotozoal. Fractionation identified the flavan-3-ol, (-)-epigallo-catechin as an active component of this plant. Previously, the polyphenols of this plant were shown to have antibacterial activity against Shigella spp. and V. cholerae [33]. Moundipa et al. [12] investigated the activity of 55 medicinal plants from Cameroon against E. histolytica. The plants selected for investigation have been used to cure jaundice and other liver disease, given that invasion of the liver by parasites can lead to the development of hepatic amoebiasis. Many plants showed activity, with the best being Codiaeum variegatum, which displayed activity greater than that of metronidazole, the reference antiprotozoal drug.

Many herbs have been used as traditional treatments for diarrhea. The uses of bayberry (see below), clove, Syzygium aromaticum (Myrtaceae), peppermint, Mentha piperita (Lamiaceae), and yarrow, Achillea clavennae (Asteraceae), are supported by laboratory studies indicating that plant components and essential oils are active against diarrheal pathogens [10, 34, 35].

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