**3.1 Experimental models**

Rodents are commonly used to induce experimental diarrhea and to study mechanisms of action of plants and their active principles. Castor oil, Prostaglandin E2 (PG-E2) and heat-labile enterotoxin are commonly used agents to induce diarrhea in animals. The diarrhoeal effect of castor oil is mediated through ricinoleic acid which causes irritation and inflammation of intestinal mucosa, and consequesntly leads to the stimulation of intestinal motility and increased secretion of fluid and electrolytes. This model is ideal to study the antisecretory and antimotility potential of medicinal plants. Prostaglandin E2 causes enteropooling by stimulating fluid secretion and increasing propulsive activity in the colon (Pierre et al., 1991). Heat-labile enterotoxin (LT) is the virulent factor of *Escherichia coli* and diarrhea by accumulation of salt and water in the intestinal lumen (Spangler., 1992). Therefore, the LTinduced diarroheal model is suitable to study inhibitory effects of plant extracts on bacterial toxins. In addition, the charcoal meal test and charcoal-gum acacia-induced hyperperistalsis in animals are helpful to identity the effect of potential medicinal plants on intestinal motility.

#### **3.2 Plants tested for antidiarrheal activity in animal models of diarrhoea**


Pharmacology of Traditional Herbal Medicines and Their Active Principles

IL-1, IL-6 and nitric oxide) (Cho et al., 2011).

mice (Zaware et al., 2011).

Used in the Treatment of Peptic Ulcer, Diarrhoea and Inflammatory Bowel Disease 303

 *Vitex negundo* is a shrub that grows in Southeast Asia. Traditionally its roots are used in the treatment of ulcerative colitis in India. Ethanolic extract of *V. negrundo* significantly inhibited acetic acid ulcerative colitis and reduced colonic MPO and MDA levels in

 *Pistacia lentiscus* is a dioecious shrub that grows in the Mediterranean region. Oleogum resin from *P. Lentiscus* is used in traditional Iranian medicine to treat IBD. Treatment with oleogum resin from *P. Lentiscus* improved the symptoms of dextran sulfate sodium (DSS) induced colitis in mice (Kim & Neophytou, 2009). A pilot study conducted in mild to moderate Crohn's disease patients demonstrated that mastic (resin) from *P. Lentiscus* significantly reduced disease activity index, plasma IL-6 and Creactive protein (Kaliora et al., 2007a) and TNFα in peripheral blood mononuclear cells (Kaliora et al., 2007b). In addition, total antioxidant potential was significantly increased. No side effects are observed in mastic treated patients (Kaliora et al., 2007a). A double-blind clinical trial in patients with duodenal ulcers exhibited symptomatic relief in 80% patients on mastic and 50% patients on placebo, while endoscopically

proven healing occurred in 70% patients on mastic (Al-Habbal et al., 1984).

ulcerative colitis (Ferna´ndez-Ban˜ ares et al., 1999).

control group in disease remission (Holtmeier et al., 2011).

**5. Quality, efficacy and safety of herbal medicines** 

**5.1 Quality** 

 *Plantago ovata* is a well-known medicinal plant in the treatment of IBD. *P. ovate* seeds ameliorated the development of colonic inflammation in transgenic rats as evidenced by an improvement of intestinal cytoarchitecture, significant decrease in some of the pro-inflammatory mediators and higher production of short-chain fatty acids (Rodŕguez-Cabezas et al., 2003). An open label, parallel-group, multicenter, randomized clinical trial in patients with ulcerative colitis concluded that *Plantago ovata*  seeds (dietary fiber) might be as effective as mesalamine to maintain remission in

 *Boswellia serrata*, a tree which grows in the hilly areas of India, is an efficacious remedy for IBD in traditional Iranian medicine and also it has been used in the Ayurvedic medicine for the treatment of inflammatory diseases. Despite its traditional claims, *Boswellia* extracts are ineffective in ameliorating colitis in DSS-induced colitis in mice (Kiela et al., 2004). In contrast to animal studies, a double-blind, randomized, placebocontrolled, multicenter trial in colitis patients showed higher remission in Boswellia serrata extract treated group than in the pacebo group (Madisch et al., 2007). However, a recent double-blind, placebo-controlled, randomized, parallel study in patients with Crohn's disease has shown no difference between the Boswellia treated group and

The quality of herbal medicines is important to ensure their safe use and efficacy. In contrast to well characterized conventional medicine, assurance of the quality of herbal medicine is a major concern. The problems associated with the herbal products include deliberate or accidental inclusion of prohibited or restricted ingredients, substitution or adulteration of herbal materials, contamination with toxic substances and differences between labelled and actual contents (Barnes et al., 2nd ed). However, increased consumer awareness and

also suppressed colonic MPO accumulation and pro-inflammatory mediators (TNFα,

 *Punica granatum* is a deciduous shrub or small tree that is native to the Himalayas in north Pakistan and Northern India. Bark, rind of the fruit and seeds of this plant are used in folk medicine to treat diarrhea. Methanol extract of seeds of *P. granatum* dose dependently reduced castor oil induced diarrhea. It also significantly inhibited gastrointestinal motility and PGE2 mediated enteropooling in rats (Das et al., 1999).


Table 2. Plants and their active constituent(s) with anti-diarrheal activity
