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

In contrast to the studies described in the previous section, the plants investigated below have been validated as treatments for diarrhea on the basis of their ability to prevent or ameliorate diarrheal symptoms induced in experimental animals or tested in clinical trials. As in the previous section, phytochemical analysis of plant preparations and identification of active components has helped to explain the mechanism of antidiarrheal activity.

The roots of Jatropha curcus (Euphorbiaceae) are used traditionally in the western coastal areas of India to control dysentery and diarrhea [36]. Methanol extracts showed dose-dependent inhibition of castor oil-induced diarrhea and intraluminal fluid accumulation, as well as small intestinal transit. This extract may act by inhibiting prostaglandin and reducing small intestinal propulsive movement. In a sim ilar manner, Chitme et al. [7] have investigated the medicinal plant Calotropis gigantea (Asclepiadaceae). A water:ethanol (50:50) extract produced a statistically significant reduction in severity and frequency of diarrhea produced by castor oil. In addition, both castor oil-induced intestinal fluid accumulation and intestinal volume content were significantly inhibited. Numerous phytochemicals, including sugars, flavonoids, flavonol glycosides, and terpenes, which have been identified in this plant, may mediate the antidiarrheal properties, although the active component has not been defined.

Black and long peppers are used as components of antidiarrheal herbal formulations [30]. Piperine, the alkaloid constituent that is reported to have numerous pharmacological actions (Fig. 12.2), has been shown to have dose-dependent inhibitory activity against castor oil, MgSO4, and arachidonic acid-induced diarrhea, gastrointestinal transit and castor oil-induced enteropooling in mice. It is thus thought to affect the actions of these gut function modulators and act by normalizing the permeability changes of water and electrolytes.

Sangre do grado, also known as dragon's blood, is the viscous red tree sap derived from several Croton species [37]. It is used extensively by people in the Amazon River basin to treat skin disorders such as abrasions, cuts, scratches, blisters, bites, and stings, but can also taken orally, in dilute form, to treat gastrointestinal illness, including infections and diarrhea. Sangre de grado is available commercially as "Zangrado" (Rainforest Phytoceuticals, Delmar, New York, USA). Miller et al. [37] found that the action of Zangrado as a therapy for diarrhea is caused by its effect on sensory afferent neurons, as shown in assays in which guinea-pig ileum was mounted in Ussing chambers and chloride secretion was evoked by capsaicin. The authors found that Zangrado was able to attenuate the response, suggesting that the medicine acts by suppression of nonmyelinated sensory nerves, leading to selective suppression of epithelial electrolyte secretion.

Jussiaea suffruticosa (Onagraceae) is a well-known traditional medicine India, where the whole plant is reduced to pulp and steeped in buttermilk as a treatment for dysentery and diarrhea [20]. An extract of this plant has been shown to inhibit castor oil-induced diarrhea, enteropooling, and gastrointestinal motility. The incidence and severity of diarrhea, as well as the frequency of defecation and wetness of fecal droppings were reduced and the effects were comparable to those seen for standard antidiarrheal drugs. Tannins present in plant extracts may be responsible for the observed effects. Similarly, an extract of the Nigerian antidiarrheal plant, Pentaclethra macrophylla (Mimosaceae), significantly reduced fecal output of castor oil-induced diarrhea in rats, significantly reduced gastrointestinal motility in mice, and blocked contractions of guinea-pig ileum evoked by various drugs [19]. In addition, the extract exhibited antibacterial activity against E. coli, but not S. aureus.

The leaves and stem bark of Alchornea cordifolia (Euphorbiaceae) are used in African folk medicine to treat urinary, respiratory, and gastrointestinal disorders [18]. A leaf extract has been shown to ameliorate the symptoms of castor oil-induced diarrhea in rats and reduce gastrointestinal transit of a charcoal meal in mice. Measurement of the fluid volume and Na+, K+, and Cl- concentrations in tied-off rat colon indicated that the extract stimulated net water absorption and reduced electro lyte secretion. An extract of the roots of Terminalia avicennoides (Combretraceae), a traditional African medicine, produced a dose-dependent reduction of spontaneous and acetylcholine-induced contraction of rabbit jejunum, reduced gastrointestinal transit and protected mice against castor oil-induced diarrhea [21].

Black tea has antiviral activity (see above) but has also been shown to affect gastrointestinal function [38]. Hot water black tea extracts (BTE) increased upper gastrointestinal tract transit, but inhibited castor oil-induced diarrhea and intestinal fluid accumulation, and normal defecation in mice. The inhibitory effects could be prevented by naloxone, an opioid antagonist, suggesting a role of the opioid system in the antidiarrheal activity of BTE. The rhizomes of ginger, Zingiber officinale (Zin-giberaceae), are widely used for treating numerous diseases, including diarrhea. Borrelli et al. [39] investigated the effect of this herbal remedy on contractions induced by electrical field stimulation (EFS) and acetylcholine on isolated rat ileum. Ginger produced concentration-dependent inhibition of both stimulants, starting at 1 ^g mL-1 for acetylcholine-induced contractions and 300 ^g mL-1 for EFS-in-duded contractions. These observations indicated an antispasmodic effect by reducing enteric excitatory transmission and direct inhibition of smooth muscle activity.

Baccharis teindalensis (Asteraceae) is commonly used in Ecuador as an anti-inflammatory, analgesic, and antimicrobial remedy [40]. An ethanol extract showed antidiarrheal activity against castor oil-induced diarrhea in mice, at doses of 50 and 100 mg kg-1, by extending the time before the first diarrheic feces, decreasing the percentage of wet feces and decreasing the total weight of excreted feces. A number of flavonoids have been identified in the extract (Fig. 12.3) which could be responsible for the observed effects.

Sakuranetin Kaempferol 7,4'-dimethyl ether

Fig. 12.3 Flavonoids isolated from the traditional medicinal plant, Baccharis teindalensis [40].

Sakuranetin Kaempferol 7,4'-dimethyl ether

Fig. 12.3 Flavonoids isolated from the traditional medicinal plant, Baccharis teindalensis [40].

A large study by Atta and Mouneir [41] reported on the antidiarrheal properties of six Egyptian medicinal plants. At a dose of 200 mg kg-1, only some of the plant extracts showed a significant effect on castor oil-induced diarrhea in rats, while the effects were better with an increased dose of 400 mg kg-1. Some of the extracts induced a dose-dependent relaxation of rabbit duodenal smooth muscle while others increased the contractile force in contractions. Various phytochemicals were identified, including tannins, flavonoids, unsaturated sterols, triterpenes, carbohydrates, lactones, proteins/amino acids, and saponins, although the active ingredients were not confirmed. Similarly, several medicinal plants used by people in the Democratic Republic of Congo [42], India [43], and Zulu traditional healers [44] to treat diarrhea have been evaluated. These plants showed activity that supported their traditional use, including activity against enteric pathogens, and activity in experimental models of diarrhea in mice or rats.

A number of plants that have been used as traditional medicines in Africa for the treatment of diarrhea and dysentery have been recently described in detail by Mueller and Mechler [45], but only those for which experimental or clinical studies support the traditional use are summarized here:

• The flesh of the fruit of the baobab tree, Adansonia digitata (Bombacaeae), is eaten raw as a treatment for diarrhea and dysentery. A clinical study in Senegal compared Adansonia fruit with ORT (82 children in each group) and found no significant difference between the two treatments in terms of duration of diarrhea and increase in weight, thus confirming the efficacy of the traditional medicine. The astringent constituents of the fruit may explain the medicinal properties, although the high levels of tartaric acid can lead to gastrointestinal irritation if large quantities of fruit are consumed.

• Euphorbia hirta (Euphorbiaceae) is used widely in Western Africa for the treatment of diarrhea. The active constituent, quercitrin, is able to reduce diarrhea induced by castor oil and prostaglandin E2 in mice (see below). Clinical studies have supported the use of E. hirta extracts for the treatment of amoebic dysentery, where 83.3% of patients in one study and 92.5% in another treated with an ethanol extract of the plant were cured.

• The bark, root, or leaves of the mango tree, Mangifera indica (Anacardiaceae), are macerated or made into decoctions or teas. The preparations are drunk or used as enemas to treat diarrhea. The high tannin content of the leaves and bark may explain the relief provided for the condition due to astringent and anti-inflammatory effects. However, there are no clinical studies to support this.

• Teas, decoctions, or macerations of the leaves of the guava tree, Psidium guajava (Myrtaceae), are well known as treatments for diarrhea in tropical countries (see above). Independent experimental studies in mice support the use of decoctions of dried leaves and aqueous extracts of leaves to treat diarrhea, although no clinical studies have confirmed these observations. The active component is believed to be quercitrin (Fig. 12.4).

Fig. 12.4 The flavonoids ternatin [46] and quercitrin [17] have antidiarrheal activity, while myricitrin is antibacterial [47].

• Decoctions or extracts of the leaves of pomegranate, Punica granatum (Punica-ceae), are used in many countries to treat diarrhea. In the Chinese pharmacopeia, the skins of fruit are recommended. The high tannin and alkaloid content of the skins are possibly responsible for the antidiarrheal effects. An orally administered methanol extract of the seeds, containing steroids, flavonoids, and tannins, has been shown to significantly reduce the frequency of stools and reduce gastrointestinal motility in mice. No clinical studies are available to support the experimental studies. The alkaloids found in all parts of the plant mean that high doses of P. granatum are toxic. Methanol and water extracts of this plant have recently been shown to have significant antimicrobial activity against ente-ropathogens [25].

• The leaves, roots, and seeds of paw paw, Carica papaya (Caricaceae), are used to treat bloody diarrhea, although no experimental studies or evidence of efficacy are available. In support of this, the studies by Alanis et al. [25] and dos Fer-nandes Vieira et al. [26] mentioned above indicated that paw paw extracts were not effective against common diarrheal pathogens. Similarly, although used in Uganda and Congo, there is no experimental or clinical evidence for the efficacy of the leaves of the passion flower, Passiflora incarnata (Passifloraceae), for the treatment of diarrhea.

12.5

Phytochemical Analysis, Identification of Active Plant Components, and Mechanism of Action of Medicinal Plants Used in the Treatment of Diarrhea

Phytochemical screening of plants extracts (made in organic solvents or water) has revealed the presence of numerous chemicals including alkaloids, tannins, flavo-noids, sterols, terpenes, carbohydrates, lactones, proteins, amino acids, glycosides, and saponins (Table 12.1). Of these, tannins, pheolics, saponins, alkaloids, and flavonoids have been linked or suggested to be involved with antibacterial and antiviral activity, while tannins and flavonoids are thought to be responsible for antidi-arrheal activity. Investigations of the mode of action indicate that tannins and flavonoids increase colonic water and electrolyte reabsorption and other phytochemi-cals act by inhibiting intestinal motility, while some components have been shown to inhibit particular enteropathogens.

The essential oil of Satureja hortensis (Laminaceae), an Iranian traditional medicine, is thought to act as an antispasmodic due to its high content of the phenolic carvacrol [48] (Fig. 12.5, Table 12.1). In contrast, analysis of the antidiarrheal constituents of Eglete viscose (Compositae), a traditional Brazilian medicine, and Euphorbia hirta (Euphorbiaceae), used widely in Africa and Asia, has identified the flavonoids ternatin and quercitrin, respectively, as the active constituents [17, 46] (Fig. 12.4, Table 12.1). Phytochemical analysis of a number of medicinal plants commonly found along the Mediterranean coast and used to treat diarrhea identified tannins and flavonoids as the likely active antidiarrheal constituents as these were found in all plants tested [49]. Yavada and Jain [50] have recently identified a new flavone glycoside, 5,7,4'-trihydroxy-6,3'-dimethoxy flavone-7-O-a-L-arabinopy-

Fig. 12.5 Carvacrol, a major component of the essential oil of Satureja hortensis, is a phenolic with antispasmodic activity.

H3C CH3

H3C CH3

Carvacrol (2-methyl-5-(l-methylethyl) phenol)

Table 12.1 Phytochemical components and mechanism of action of selected medicinal plants used to treat diarrhea.[a]

Plant(sj

Phytochemicals identified

Phytochemical(s) with bioactivity Mechanism of action

Alchornea cordifolia

Anacardium occidentale

Artocarpus integrifolia Myristica fragrans Psidium guajava Spondias lutea Spongias lutea Calotropis gigantea

Cissus rubiginosa Cocos nucifera

Egletes viscosa

Epinetrum villosum Euphorbia hirta

Pentaclethra macrophylla

Roureopsis obliquifolia Satureja hortensis essential oil Terminalia avicennoides

Alkoloids, tannins, saponins, flavonoids, phenols

Tannins, flavonoids, terpenes, saponins

Flavonoids, terpenes, nitrogen compounds

Flavonoids

Tannins, flavonoids

Flavonoids

Tannins, flavonoids

Sugars, flavonoids, flavonol glycosides, oxypregnane-oligoglycosides, terpenes and terpene derivatives

Flavonoids, tannins

Tannins

Alkaloids, saponins

Flavonoids, reducing sugar, tannins, glycosides

Flavonoids, saponins, tannins Major constituents are carvacrol (33.7%) and Y-terpinene (31.8%) Saponins, tannins, flavonoids

Not known, possibly tannins and flavonoids

Possibly flavonoids, as these are common components

Not known

Probably tannins Catechin, epicatechin, B-type procyanidins Ternatin (flavonoid)

Probably alkaloids Quercitrin (flavonoid)

Not known

Probably tannins and saponins Probably carvacrol (phenolic)

Not known

Antidiarrheal; stimulation of net water absorption and reduction in electrolyte secretion

Antiviral; inhibition of rotavirus propagation

Antidiarrheal; altered activity of Na+K+ATPase or activation of chloride channels and reversal of chloride secretion? Antimicrobial; mechanism unknown Antibacterial; mechanism unknown

Antidiarrheal; inhibition of intestinal transit, secretion and motility; interference with cellular enzyme and neurotransmitter systems or interaction with calcium channels? Antimicrobial; mechanism unknown Antidiarrheal; modulation of arachidonic metabolism via inhibition of cyclo-oxygenase and lipoygenase?

Antidiarrheal; musculotropic; limits availability of Ca2+ at steps involved in excitation-contraction coupling? Antimicrobial; mechanism unknown Antispasmolytic; inhibition of contractile overactivity of the ileum Antidiarrheal; inhibition of spontaneous and agonist-induced contractions of jejunum fi f A

a Other plants are described in the text.

ranosyl-(1^6)-0-p-D-galactopyranoside from Melilotus indica (Leguminosae), a medicinal plant used in various applications, including the treatment of infantile diarrhea, found in India, the Middle East, and Europe. This compound was found to exhibit antibacterial activity against pathogens that caused diarrhea.

Herbs with astringent properties, such as meadowsweet, Filipendula ulmaria (Rosaceae), agrimony, Agrimonia eupatoria (Rosaceae), shepherd's purse, Capsella

Theaflavin-3' monogallate Theaflavin-3,3' digallate

Fig. 12.6 Theaflavin and gallate derivatives are polyphenols compounds extracted from black tea which neutralize bovine rotavirus [14].

Theaflavin-3' monogallate Theaflavin-3,3' digallate

Fig. 12.6 Theaflavin and gallate derivatives are polyphenols compounds extracted from black tea which neutralize bovine rotavirus [14].

bursa-pastoris (Cruciferae), and cranesbill, Geranium maculatum (Geraniaceae), are suggested to be useful as they bind to the mucosal lining of the small intestine [32]. Herbs that contain the alkaloid berberine (Fig. 12.2), for example goldenseal, Hydrastis canadensis (Ranunculaceae), and barberry, Berberis vulgaris (Berberidaceae), have an antimicrobial effect [51] and may also be helpful. Bayberry, Myrica cerifera (Myricaceae), contains the antibacterial compound myricitrin (Fig. 12.4), which may explain why it is a useful treatment for diarrhea [47]. As mentioned earlier, crude black tea extracts, theaflavins, and theaflavin gallate derivatives are able to neutralize rotavirus in vitro [14]. The structures of these polyphenolic compounds are shown in Fig. 12.6.

Numerous phytochemicals have demonstrated antibacterial activity and the various mechanisms of action have been described by Cowan [51]. Phenolics are a broad class of compounds that have a variety of antibacterial mechanisms. The following subclasses have specific mechanisms of action. Simple phenols such as catechol and epicatechin work by substrate deprivation and membrane disruption, respectively; phenolic acids and quinones bind to adhesins, complex with the cell wall and inactivate enzymes; flavonoids bind to adhesins; flavones complex with the cell wall; and tannins bind to proteins and adhesins, inhibit enzymes, complex with the cell wall, disrupt membranes, complex metal ions, and work by substrate deprivation. The mechanism of action of flavonols in unknown. Other classes of antibacterial phytochemicals include terpenoids, such as capsaicin, and essential oils which act by membrane disruption and alkaloids, such as berberine and piperine, which intercalate into the cell wall and/or DNA.

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Reiki 101

Reiki 101

Looked upon as a mysterious practice, reiki originated from Japan, around 1922. Started by a Japanese Buddhist, this practice of purported healing basically uses the palm of an individual to emit positive healing energy unto the patient. Sometimes reiki is referred to as oriental style treatment by professional medical bodies.

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