**Pharmacology of Traditional Herbal Medicines and Their Active Principles Used in the Treatment of Peptic Ulcer, Diarrhoea and Inflammatory Bowel Disease**

Bhavani Prasad Kota1, Aik Wei Teoh2 and Basil D. Roufogalis1 *1University of Sydney 2Ferngrove Pharmaceuticals Australia* 

### **1. Introduction**

296 New Advances in the Basic and Clinical Gastroenterology

U.S. Food and Drug Administration (2006). Center for Drug Evaluation and Research.

Verheij, M.H.; Westerman, J.; Sternby, B. & de Haas, G.H. (1983). The complete primary

Vuoristo, M.; Vaananen, H.; Miettinen, T.A. (1992). Cholesterol malabsorption in pancreatic

Walker-Smith, J.; Barnard, J.; Bhutta, Z.; Heubi, J.; Reeves, Z. & Schmitz, J. (2002). Chronic

Walters, M.P. & Littlewood, J.M. (1996). Pancreatin preparations used in the treatment of

Whitcomb, D.C. & Lowe, M.E (2007).Human pancreatic digestive enzymes. *Digestive* 

Winkler, F.K.; D'Arcy, A. & Hunziker, W. (1990). Structure of Human pancreatic lipase.

Wion, K.L.; Kirchgessner, T.G.; Lusis, A.J.; Schotz, M.C. & Lawn, R.M. (1987). Human

Wolle, J.; Jansen, H.; Smith, L.C. & Chan, L. (1993). Functional role of N-linked glycosylation

Wooldridge, J.L.; Heubi, J.E.; Amaro-Galvez, R.; Boas, S.R.; Blake, K.V.; Nasr, S.Z.; Chatfield,

Whitcomb, D.C.; Lehman, G.A.; Vasileva, G.; Malecka-Panas, E.; Gubergrits, N.; Shen, Y.;

Whitcomb, D.C. & Lowe, M.E. (2007). Human pancreatic digestive enzymes. *Digestive* 

Yasuda, T.; Ishida, T. & Rader, D.J. (2010). Update on the Role of Endothelial Lipase in High-

Zentler-Munro, P.L.; Fitzpatrick, W.J.; Batten, J.C. & Northfield, T.C. (1984). Effect of

Atherosclerosis. *Circulation Journal*, Vol. 74, pp. 2263 – 2270.

secretion. *Journal of Lipid Research.* Vol. 34, pp. 2169–2176.

lipoprotein lipase complementary DNA sequence. *Science,* Vol. 235, pp. 1638–1641.

in human hepatic lipase: asparagine- 56 is important for both enzyme activity and

B.; McColley, S.A.; Woo, M.S.; Hardy, K.A.; Kravitz, R.M.; Straforini, C.; Anelli, M. & Lee, C. (2010). EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. *Journal of Cystic Fibrosis.* 

Sander-Struckmeier, S. & Caras S. (2009). Pancrelipase Delayed-Release Capsules (CREON) for Exocrine Pancreatic Insufficiency due to Chronic Pancreatitis or Pancreatic Surgery: A Double-Blind Randomized Trial. *The American Journal of* 

Density Lipoprotein Metabolism, Reverse Cholesterol Transport, and

intrajejunal acidity on aqueous phase bile acid and lipid concentrations in pancreatic steatorrhoea due to cystic fibrosis. *Gut.* Vol.25, No. 5, pp. 500- 507.

2006. Accessed March 9 2009.

Vol. 747, No. 1–2, pp. 93–99.

*Therapeutics*. Vol. 10, No. 3, pp. 433-440.

*Nature*, Vol. 343, pp.771-774.

Vol. 8, No. -, pp. 405- 417.

*Gastroenterology,* Vol. 105, pp. 2276-2286.

*diseases & Sciences*. Vol. 52, N°. 1, pp. 1-17

*Diseases & Sciences,* Vol. 52, No. 1, pp. 1-17.

105.

Guidance for Industry: Exocrine Pancreatic Insufficiency Drug Products— Submitting NDAs. *http://www.fda.gov/cder/guidance/6275fnl.htm.* Published April 13,

structure of phospholipase A2 from human pancreas. *Biochimica & Biophysica Acta*.

insufficiency: effects of enzyme substitution. *Gastroenterology*. Vol. 102, pp. 647–655.

Diarrhea and Malabsorption (Including Short Gut Syndrome): Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. *Journal of Pediatric Gastroenterology and Nutrition*,Vol 35, No. 2, pp. 98–

cystic fibrosis-lipase content and in vitro release. *Alimentary Pharmacology &* 

The endocrine, exocrine and paracrine secretions of the gastrointestinal (GI) tract play a pivotal role in the digestion and absorption of food and orally administered drugs. The secretion of mucus by mucus-secreting cells protects the erosion of the gastric mucosa from the highly acidic gastric juice. The secretion of hydrochloric acid from parietal cells is regulated by acetylcholine, histamine and gastrin. Disturbances in secretory functions of the gastrointestinal tract can lead to several GI complications. Conventional therapies employ a range of drugs that have been pharmacologically well characterised. While these drug molecules are proven to be beneficial, the adverse effects and drug-drug interactions highlight the need for better treatment modalities for GI tract disorders.

Since ancient times, herbal medicines have been traditionally used to treat several diseases. The gastroprotective properties of these herbs and their active constituents have been experimentally demonstrated (Al Mofleh, 2010). Asian traditional medicine systems have identified several herbs and spices to treat GI tract disorders (Langmead & Rampton, 2006; Sengupta et al., 2004). In support of these traditional claims, several preclinical and clinical studies have provided the scientific basis for the effectiveness of herbal extracts (e.g. *Glycyrrhiza glabra*) and their active constituents (e.g. flavonoids) in treating GI tract disorders (Borrelli & Izzo, 2000). The discovery and development of anti-ulcer agents such as carbenoxolone from *Glycyrrhiza glabra* and gefarnate from cabbage further highlight the presence of pharmacologically active components in herbal extracts and suggests their use as an alternative therapy to treat GI tract disorders.

The effectiveness and the mechanisms of action of crude herbal extracts vary according the composition of their chemical constituents. Herbal medicine seems to fill this gap, especially when employing high manufacturing standardised forms of herbal medicine with regard to the quality and quantity of ingredients (Suzuki et al., 2009). In addition, well characterised herbal formulations may lead to the production of reliable clinical data on efficacy and safety. As several studies have shown that herbal medicines may produce adverse reactions and herb-

Pharmacology of Traditional Herbal Medicines and Their Active Principles

mucus (Antônio & Souza Brito, 1998).

against *Helicobacter pylori* (Germano` et al., 1998).

agents (0.2 N NaOH and 80% ethanol) (Liu et al., 2001).

al., 2002).

are attributed to the presence of flavonoids, sterols and triterpines.

Used in the Treatment of Peptic Ulcer, Diarrhoea and Inflammatory Bowel Disease 299

 *Turnera ulmifolia* or 'chanana' (Turneraceae) is a small herb with wide geographical distribution ranging from Guyana to the North Eastern region of Brazil. It is a widely used folk medicine for its anti-inflammatory properties. The hydroalcoholic extract of *T*. *ulmifolia* inhibited gastric lesions induced by pylorus ligature, by indomethacin and by ethanol, but stress mediated lesions remained unaffected. As histamine plays a role in ulcerogenesis in pylorus ligation, it was postulated by the study authors that *T*. *ulmifolia*  exerts gastroprotective actions by inhibiting histamine. The inhibition of gastric ulcers induced by indomethacin and ethanol indicate that gastroprotective effects of *T*. *ulmifolia* could be due to an enhancement of mucosal defensive factors such as gastric

 *Dodonaea viscosa* is a stiff bushy plant. Tribes who reside in the forest regions of South India (Kerala) use leaves of this plant for headaches and backaches. The hexane extract of *Dodonaea viscosa* dose dependently inhibited ethanol and indomethacin induced gastric lesions. Gastric secretion studies showed significant decrease of total acid in gastric juice (Arun & Asha, 2008). Furthermore, it decreased total acid content and

 The aqueous extract of Neem bark when administered for 10 days at 30 mg dose twice daily significantly inhibited gastric acid secretion in patients with chronic gastric acid problem. The bark extract completely healed the duodenal ulcers at the dose of 30-60 mg twice daily for 10 weeks (Bandyopadhyay et al., 2004). Some important blood parameters for organ toxicity such as sugar, urea, creatinine, serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, albumin, globulin, hemoglobin levels and erythrocyte sedimentation rate remained unaffected upon Neem exposure. *Pteleopsis suberosa* is traditionally used in Mali for the treatment of gastric ulcers. The aqueous extract of *P. suberosa* exhibited protective effects on gastric mucosa in ethanol and indomethacin treated rats (De Pasquale et al., 1995). It has also been shown that *Pteleopsis suberosa* decoction containing triterpenoid saponins and tannins is effective

 *Calligonum comosum* is a shrub distributed throughout Arabia and growing in sandy deserts. It is used by the local healers to treat stomach ailments. Pre-treatment with the 10% ethanolic extract displayed a significant and dose-dependent inhibition of acute gastric ulcers induced by NSAIDs (phenylbutazone and indomethacin) and necrotic

 *Solanum torvum*, a small tree, is widely used in African folk medicine to treat various diseases including gastric ulcer (Noumi et al., 2000). Aqueous and methanolic extracts from

increased gastric glutathione levels in ethanol and indomethacin treated rats. *Azadirachta indica* is a native tree to the Indian subcontinent. To the Indian it is commonly known as Neem and regarded as a 'village dispensary' due its multiple therapeutic properties. It has been extensively used in Ayurveda, Siddha, Unani and other local Indian folklore medicine systems (Brahmachari, 2004). Standardized aqueous extract of Neem exhibited remarkable anti-ulcer activity in restraint-cold stress and indomethacin induced gastric ulcers in rats. Animal studies suggest that the major gastroprotective effect of Neem bark extract against ulcer is mediated through inhibition of acid secretion by H+-K+-ATPase and prevention of oxidative damage (Bandyopadhyay et

significantly replenished gut wall mucous and reduced malondialdehyde (an indicator of lipid peroxidation) levels in ethanol treated rats. Gastroprotective effects of Rocket

drug interactions, the common assumption that 'herbal products are natural, they are safe' is no longer valid. Safety and quality data of herbal medicines should be made available to medical practitioners and other healthcare professionals to avoid these unwanted effects.

Several plants have been used by traditional healers around the world to treat various gastrointestinal tract diseases. Centuries ago the reliance on nature to cure human ailments was developed by great efforts of dedicated professionals by keen observation and trial and error method. This important knowledge is updated constantly and passed from generations to generations. Today traditional healing systems play important roles in several parts of the world, especially where modern pharmaceuticals are less accessible. Modern scientific research methods are invaluable to support traditional claims and also to develop traditional remedies as a viable alternative to mainstream pharmaceuticals. In recent years, a number of research papers have been published on herbal medicines to provide the experimental evidence for their traditional claims. Given the multitude of these research publications, it is not possible to cover all of them. In this chapter, we only attempted to provide the experimental (animal and human studies) evidence for the plants that have been traditionally used to treat most notable gastrointestinal diseases, namely, peptic ulcer, diarrhoea and inflammatory bowel syndrome.
