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Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases
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Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review R. Arora⁎,†, P. Malhotra†, S. Sundriyal†, H.S. Yashavanth‡, R.J. Pai‡, M.S. Baliga‡ ⁎
Chief Controller Research and Development (Life Sciences and International Cooperation), New Delhi, India Institute of Nuclear Medicine and Allied Sciences, Delhi, India Father Muller Medical College, Mangalore, India
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1. INTRODUCTION The gastrointestinal tract (GIT) is anatomically an extensive tubular tract extending from the mouth to the anus, with accessory organs such as the salivary glands, pancreas, and hepatobiliary system. The gut is in physical continuity and is compartmentalized by thick sphincters, which carry out their specialized function under the control of the neurohormonal system. The GIT performs the important function of assimilation, absorption of nutrients, and elimination of the waste, and its optimal functioning is very essential for the optimal health of the individual (Feldman et al., 2006). The GIT is a sensitive organ and may be affected by various factors, both endogenous and exogenous. Some of the mild ailments include dyspepsia, altered bowel habits, acid peptic disease, gastroesophageal reflux disease, lactose intolerance, celiac disease, microbial infection, and worm infestation; the severe ones include the inflammatory bowel diseases (IBDs), chronic diarrhea, and cancer (Feldman et al., 2006). A number of drugs are available for the treatment of various gastrointestinal ailments/ diseases. However, the clinical evaluation of these drugs has shown the incidence of relapses and side effects (Feldman et al., 2006; Table 19.1). This has necessitated the need for nontoxic drugs that are effective and devoid of side effects, and medicinal plants are being actively investigated, especially in the preclinical models of study.
2. HERBAL DRUGS IN GASTROINTESTINAL AILMENTS/DISEASES According to the World Health Organization, more than three-fourths of the world population still uses herbal preparations for various day-to-day ailments. Treatment for gastrointestinal disorders consists in the use of herbal supplements for symptomatic relief and improvement in the physiologic function of the GIT. Surveys of varying design and quality among the general population have shown that 8–50% of people in Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease http://dx.doi.org/10.1016/B978-0-12-397154-8.00033-6
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2013 Elsevier Inc. All rights reserved.
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Table 19.1 Side Effects of the Commonly Used Drugs to Treat Various Gastrointestinal Ailments and Diseases Diseases Common drugs Common side effects
Acid peptic disease and dyspepsia
Aluminum hydroxide Magnesium hydroxide Calcium carbonate Sodium bicarbonate H2 blockers
Constipation
PPIs Sucralfate Prostaglandins Cascara sagrada and senna
Diarrhea
Phenolphthalein Osmotic laxatives Bulk laxatives Emollient laxatives Loperamide
Antispasmodics IBD
Codeine and paregoric Dicyclomine Sulfasalazine Glucocorticoids Azathioprine and 6-mercaptopurine Methotrexate
Antiprotozoal
Metronidazole
Antihelminthics
Mebendazole Albendazole Pyrantel pamoate Ivermectin Fluoroquinolones (ciprofloxacin) Macrolides (erythromycin) Aminoglycosides (gentamicin) Cephalosporins (ceftriaxone) Aminopenicillins (amoxicillin) 5-Fluorouracil Cisplatin Irinotecan
Antibacterial
Anticancer drugs
Constipation Loose stools Milk-alkali syndrome Systemic alkalosis Gynecomastia, impotence (cimetidine), levels of creatinine, transferases Hypochlorhydria, carcinoid tumor Constipation Diarrhea, uterine bleeding Excessive purgation and melanotic pigmentation of the colonic mucosa Carcinogenicity CNS depression Intestinal obstruction Granulomatous fibrosis Abdominal cramps, paralytic ileus (in children) Addiction Urinary hesitancy, drowsiness Allergic reactions, hepatitis, pancreatitis, agranulocytosis Fluid retention, fat redistribution, hyperglycemia, osteonecrosis Pancreatitis, lymphoma Leucopenia, hepatic fibrosis, hypersensitivity pneumonitis Metallic taste, abdominal cramps, thrombophlebitis (IV route) Nausea, allergic reactions, teratogenic Alopecia, neutropenia on prolonged use Anorexia, raised plasma SGOT levels Pruritus, arthralgia Juvenile arthropathy, dizziness Hepatitis, arrhythmias, allergic reaction Ototoxicity, nephrotoxicity Hypersensitivity, nephrotoxicity Diarrhea, rashes Pancytopenia, toxic CNS effects Ototoxicity Diarrhea, neutropenia, and thrombocytopenia
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
Western Europe and the United States have used some form of complementary therapy (Arora, 2010). In developing countries, the usage is even more widespread. Well-conducted random telephone surveys in the United States showed that the use of complementary and alternative medicine rose from 34% in 1990 to 42% in 1997. The single most widely used modality in 1997 was herbal medicine, which showed a 380% increase from 7 years earlier (Langmead and Rampton, 2001). India has a rich tradition of using plants to treat various ailments, and the Indian traditional systems of medicine, Ayurveda, Siddha, and Unani, as well as the innumerable folk medicines, utilize plants to treat various ailments, including gastrointestinal ailments and diseases. This chapter collates the scientific observations of various investigators on the gastroprotective effects of some commonly used medicinal plants (Figure 19.1) on the mechanisms responsible for the protective effects.
2.1 Aegle marmelos Commonly known as bael, A. marmelos is a tree originally indigenous to India but is today found growing in Pakistan, Sri Lanka, and other Southeast Asian countries. In Ayurveda, bael is utilized for its ability to treat an assortment of diseases, including diarrhea, dysentery, and dyspeptic symptoms. Marmelosin, isolated from the bael plant, has been reported to have antihelminthic and antibacterial activity. Various other constituents Trigonella foenum-graecum Aegle marmelos
Withania somnifera
Boswellia serrata
Mentha arvensis
Zingiber officinalis
Curcuma longa
Garcinia cambogia
Aloe arborescens Tinospora cordifolia
Picrorhiza kurroa
Punica granatum
Commiphora molmol Centella asiatica
Figure 19.1 Plants with scientifically validated gastrointestinal protective effects.
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and the presence of tannin and other mucilaginous substances have been detected in the plant. Some researchers have also observed beneficial effects in luvangetin, a pyranocoumarin obtained from the seeds of the bael plant, in the treatment of gastric ulceration. Preclinical studies with rats have shown that the extract of unripe bael fruit (50 and 100 mg kg1, ip) was effective in reducing ethanol-induced gastric ulceration but ineffective in other models of ulcerogenesis (hypothermic restraint stress and indomethacin). The extract was also effective in inhibiting castor oil-induced diarrhea, intestinal transit, as well as the accumulation of intestinal fluids in mice (Dhuley, 2003).
2.2 Aloe vera or Aloe arborescens Aloe vera is a medicinal plant since centuries and is accredited to promote intestinal motility and relieve constipation. Studies have shown that oral intake of aloe vera for 4 weeks affords clinical respite in patients suffering from ulcerative colitis. The Aloe vera gel has been validated to protect against gastric ulceration (Eamlamnam et al., 2006). Preclinical studies have shown that the ethanolic extract of Aloe vera was effective in reducing the acute gastric mucosal lesions produced by 0.6 M HCl and the acid output in pylorusligated and lumen-perfuse rats. The extract decreased the secretion of acid (Yusuf et al., 2004). Additionally, aloctin A, a glycoprotein isolated from the leaves also inhibited the volume of gastric juice, acid, and pepsin output in pylorus-ligated rats. It was also effective in inhibiting the development of Shay ulcers and indomethacin-induced gastric lesions as well as in inhibiting water-immersion stress lesions induced in pylorus-ligated rats (Saito et al., 1989).
2.3 Boswellia serrata B. serrata is an important Indian medicinal plant, and studies have shown that boswellic acid was effective in various gastrointestinal ailments. Scientific studies have shown it to be effective in ameliorating 2,4,5-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats (Latella et al., 2008) and in patients with ulcerative colitis (Gupta et al., 1997, 2001). Additionally, studies have shown that the semisynthetic form of acetyl-11keto-b-boswellic acid, an active principle of B. serrata, also prevented dextran sodium sulfate (DSS)-induced experimental murine colitis as assessed by gross and histological observations (Anthoni et al., 2006). The gum resin extract is also reported to reduce the electrically, acetylcholine-, and barium chloride-induced contractions in the isolated guinea pig ileum and to inhibit the upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhea (Borrelli et al., 2006). Boswellic acids, the active compounds, are also reported to possess antiulcer effects in the pyloric ligation, ethanol/HCl, (acute and chronic) acetylsalicylic acid, indomethacin, and cold restraint stress models of study (Singh et al., 2008).
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
2.4 Centella asiatica C. asiatica, commonly known as brahmi, is a small herbaceous annual plant of the family Mackinlayaceae. It is a mild adaptogen, mildly antibacterial, antiviral, anti-inflammatory, antiulcerogenic, anxiolytic, and a cerebral tonic, a circulatory stimulant, a diuretic, nervine, and vulnerary. The extract of C. asiatica is reported to inhibit the gastric ulceration induced by cold and restraint stress, and the effect was comparable to that of famotidine (H2 antagonist; Chatterjee et al., 1992). The fresh juice of C. asiatica is reported to be effective against ethanol-, aspirin-, cold restraint stress-, and pyloric ligation-induced gastric ulcers in rats. The drug increased the gastric juice mucin secretion and increased the mucosal cell glycoproteins signifying increase in cellular mucus. It also decreased cell shedding indicating fortification of mucosal barrier (Sairam et al., 2001).
2.5 Commiphora molmol C. molmol, commonly known as guggal, guggul, or mukul myrrh tree, is a flowering plant of the family Burseraceae. It is found from Northern Africa to Central Asia but is most common in northern India. The tree exudes a yellowish resin called gum guggul or guggulu, which has a balsamic odor. Guggul gum is useful in the treatment of lipid disorders, acne vulgaris, arthritis, and obesity. Studies have shown that aqueous suspension of the oleogum resin of C. molmol (250, 500, and 1000 mg kg1) was effective in protecting the gastric mucosa against the ulcers caused by 80% ethanol, 25% NaCl, 0.2 M NaOH, indomethacin, and combined indomethacin–ethanol treatment. The protective effect observed was attributed to its effect on mucus production, increase in nucleic acid, and nonprotein sulfhydryl concentration, which appears to be mediated through its free radical-scavenging, thyroid-stimulating, and prostaglandin-inducing properties (Al-Harbi et al., 1997).
2.6 Curcuma longa Curcuma is native to tropical South Asia and is widely found in India as well. Curcumin (diferuloylmethane), the major active ingredient of turmeric, is derived from the dried roots of C. longa. Its chemical formula is 1,7-bis-(4-hydroxy-3-methoxyphenyl)1,6-heptadiene-3,5-dione. Studies have shown that it has antioxidant properties and provides symptomatic relief in patients with IBD. Curcumin has been shown to inhibit the growth of transformed cells and colon carcinogenesis at the initiation, promotion, and progression stages in carcinogen-induced rodent models (Ammon and Wahl, 1991; Ishita et al., 2004). Curcumin has been found to inhibit forestomach and colon carcinogenesis. The active principle in various extracts of turmeric and curcumin has been shown to produce antiulcerogenic activity in rats. Curcumin is also reported to prevent/reduce the ulcerative colitis in experimental models and in humans (Hanai and Sugimoto, 2009).
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2.7 Garcinia cambogia G. cambogia is a plant indigenous to India and parts of Southeast Asia. The fruits, which resemble miniature pumpkins, are of use as both dietary and medicinal agents. Animal studies have shown that the G. cambogia fruit extract (1 g kg1 body weight per day for 5, 10, or 15 days) protected the gastric mucosa against the damage induced by indomethacin (Mahendran et al., 2002a) and HCl–ethanol-induced (Mahendran et al., 2002b) gastric mucosal injury. G. cambogia decreased acidity and increased the mucosal defense in the gastric areas, decreased lipid peroxidation, increased the activity of antioxidant enzymes, altered levels of protein and glycoproteins in the ulcerated mucosa, and maintained the gastric juice at near normal levels (Mahendran et al., 2002a,b). Experiments have shown that the fruit extract inhibited the TNBS-induced colitis in rats by preventing the damage and decreasing myeloperoxidase (MPO) activity, and by the expression of COX-2 and iNOS to reduce the colonic levels of PGE2 and IL-1b, and to reduce DNA damage in the colonocytes (Dos Reis et al., 2009).
2.8 Mentha arvensis Peppermint (family: Lamiaceae) is a herbaceous rhizomatous perennial plant growing in moist habitats, including streamsides and drainage ditches. Being a hybrid, it is usually sterile, producing no seeds and reproducing only vegetatively, spreading by its rhizomes. Peppermint oil is one of the most commonly used over-the-counter remedies for gastrointestinal ailments (Pittler and Ernst, 1998). It prevents smooth muscle contractions and can be used for relief from abdominal pain associated with irritable bowel syndrome. Its antispasmodic action is achieved via influx of calcium ions across the cell membrane (Hills and Aaronson, 1991). It is therefore indicated in the treatment of abdominal pain and distension of functional dyspepsia/IBS, particularly in subjects with flatulence. On the other hand, it may have side effects such as heartburn, anal burning, and discomfort. Scientific studies have shown that the petroleum ether, chloroform, or aqueous extract (375 mg kg1 oral) was effective in preventing ibuprofen plus pyloric ligation-, 0.6 mol l1 HCl-, and 90% ethanol-induced gastric ulcerations in rats (Londonkar and Poddar, 2009). The methanolic extract is also observed to possess antibacterial effects on Helicobacter pylori in vitro (Castillo-Jua´rez et al., 2009).
2.9 Picrorhiza kurroa P. kurroa commonly known as kutki and belonging to the family Scrophulariaceae, is a herb native to the Himalayan regions of India, Pakistan, and Nepal. The roots and rhizomes are medicinally the most important parts and are in great demand in the various traditional and folk systems of medicine (Banerjee et al., 2008). The powder, decoction, infusion, confection, and alcoholic extract of the roots and rhizomes are useful in treating
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
various liver ailments: their anticholestatic effects are useful in treating dyspepsia, chronic diarrhea, and infection of the upper respiratory tract, and their antioxidant and immunemodulatory effects in treating fevers. Studies have shown that the methanolic extract of P. kurroa rhizomes was effective in reducing the indomethacin-induced gastric ulceration in mice by reducing oxidative stress; promoting mucin secretion and prostaglandin synthesis; and augmenting expressions of cyclooxygenase enzymes and growth factors (Banerjee et al., 2008).
2.10 Punica granatum P. granatum, commonly known as pomegranate, is an important medicinal plant. Studies have shown that the standardized aqueous methanolic extract of pomegranate (490 and 980 mg kg1 body weight) was effective in reducing alcohol-, indomethacin-, and aspirin-induced, and pylorus-ligated gastric ulcerations. Pomegranate extract also reduced the gastric volume and total acidity and increased the pH and mucus secretion in pylorus-ligated rats (Alam et al., 2010). The methanolic extract of the pomegranate seeds is also shown to possess antidiarrheal activity against castor oil-induced diarrhea and PGE2-induced enteropooling, and to reduce the gastrointestinal motility in charcoal meal test in rats (Das et al., 1999). The aqueous and methanolic extracts of pomegranate are also reported to be effective against Escherichia coli, Shigella sonnei, Shigella flexneri, and Salmonella sp. in vitro (Alanı´s et al., 2005). Additionally, Singh et al. (2009) observed that feeding Swiss albino mice with hydromethanolic extracts of the pomegranate flower and its ellagic acid-rich fraction (100 mg kg1 and 200 mg kg1, po) decreased the DSSinduced ulcerative colitis. The effect was comparable to sulfasalazine (100 mg kg1, po) and sodium cromoglicate (40 mg kg1, ip). Histopathological studies showed that the extracts reduced the degree of ulceration, levels of MPO, histamine, and lipid peroxides (Singh et al., 2009).
2.11 Tinospora cordifolia T. cordifolia commonly named guduchi is a herbaceous vine of the family Menispermaceae and is an important medicinal plant in Ayurveda for treating various ailments. It is an antispasmodic, analgesic, antipyretic, and anti-inflammatory agent. It is given for intermittent fevers and infective conditions such as typhoid, malaria, filariasis, and leprosy. It also has anthelmintic properties. It is prescribed for urinary disorders, skin diseases, and eye diseases. It is also used in gout and rheumatoid arthritis. It has cardiotonic, hematinic, expectorant, antiasthmatic, and aphrodisiac actions. Recently, Savrikar et al. (2010) have observed that the Ayurvedic preparation of T. cordifolia is effective in forced swimming-induced hypothermia and gastric ulceration.
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2.12 Trigonella foenum-graecum Commonly known as fenugreek, the seeds of the plants are of use as both culinary and medicinal agents in various traditional and folk systems of medicine. Studies have also shown that fenugreek seeds were effective in reducing ethanol-induced gastric ulcer and that they mediate their protective effects by their antisecretory action, increasing the mucosal glycoproteins and the antilipid peroxidative effects. Histopathological observations showed that the soluble gel fraction derived from the seeds was more effective than omeprazole in preventing lesion formation (Pandian et al., 2002). Pretreatment with diosgenin has also been shown to prevent the indomethacin-induced intestinal inflammation (Yamada et al., 1997) and to inhibit the ovalbumin-induced intestinal allergic responses; it suppressed intestinal inflammation, the occurrence of diarrhea, infiltration and degranulation of mast cells, and the presence of mucin-containing goblet cells in the duodenum in mice (Huang et al., 2009). Diosgenin also reduced the crypt depth of the intestine (Huang et al., 2009).
2.13 Withania somnifera W. somnifera, also known as ashwagandha in Hindi and as Indian ginseng and Winter cherry in English, is a plant of the Solanaceae family. In the Ayurvedic system of medicine, ashwagandha is considered beneficial in the treatment of many diseases. Preclinical studies have shown that the methanolic extract of the ashwagandha root (100 mg kg1 body weight per day orally for 15 days) was effective in reducing the indomethacin- and swim (restraint)-induced gastric ulcerations in rats and that the effects were comparable to those of the standard drug ranitidine. The extract reduced the ulcer index, volume of gastric secretion, free acidity, and total acidity. A significant increase in the total carbohydrate and total carbohydrate/protein ratio was also observed. The extract increased the antioxidant enzymes (superoxide dismutase, catalase) and ascorbic acid, and concomitantly decreased the levels of lipid peroxidation (Bhatnagar et al., 2005).
2.14 Zingiber officinale The rhizome of Z. officinale, commonly known as ginger, is an important spice and an integral part of several medicinal formulations in Ayurveda, Siddha, Unani, Sri Lankan, Greek, Roman, Asian, Indian, Mediterranean, and Arabic systems of medicines. In the various systems of medicine, ginger has been reported to possess carminative effects; it has been shown to decrease the pressure on the lower esophagus, to lessen intestinal cramping, to prevent dyspepsia, and to reduce flatulence and bloating (Ali et al., 2008; Chrubasik et al., 2005). Ginger is efficacious in preventing nausea and vomiting (Ali et al., 2008; Chrubasik et al., 2005). Multiple studies have clearly shown that whole ginger and some of its phytochemicals are potent gastroprotective agents in various standard experimental models such as the HCl/ethanol-, 80% ethanol-, 0.6 M HCl-,
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
0.2 M NaOH-, and 25% NaCl-, indomethacin-, aspirin-, reserpine-, and hypothermic restraint-induced-ulcers; the swim stress-/ethanol stress-induced ulcers; and the pylorus ligation-induced gastric ulcerations in rats (Al-Yahya et al., 1989; Nanjundaiah et al., 2009; Yamahara et al., 1988). Studies by Mahady et al. (2003) have also shown that the methanol extract of ginger, the extract fractions, and the isolated constituents, 6-,8-,10-gingerol and 6-shogoal, inhibited the growth of the different strains of H. pylori in vitro with a minimum inhibitory concentration in the range of 6.25–50 mg ml1. Scientific studies by El-Abhar et al. (2008) have shown that pretreatment with ginger extract ameliorated the acetic acid-induced edematous inflammation in the colon. Together, all these observations clearly indicate the myriad uses of ginger in the prevention and treatment of various gastrointestinal ailments.
3. CONCLUSION Preclinical studies suggest that commonly used Indian medicinal plants such as A. marmelos, Aloe vera or Aloe arborescens, P. granatum, T. foenum-graecum, B. serrata, C. longa, G. cambogia, C. molmol, C. asiatica, P. kurroa, T. cordifolia, W. somnifera, and Z. officinale are effective in ameliorating/preventing various gastrointestinal ailments. Of these, A. marmelos, B. serrata, P. granatum, T. foenum-graecum, Z. officinale, C. longa, and G. cambogia are observed to be the most promising. However, for them to be of clinical/pharmaceutical use, detailed investigations, which will bridge the gaps in the existing knowledge of these plants, are required. The three main areas of lacunas are the incompleteness of the pharmacological studies, the lack of phytochemical validation, and the lack of human studies. Detailed studies with different and more robust preclinical models on the mechanistic aspects and the active principles are required. Additionally, the phytochemicals that are responsible for the observed pharmacological properties are known to be variable depending on the plant age, part, and geographical and seasonal conditions. Studies should be performed with well-characterized extracts with the knowledge of the levels of their different vital bioactive components as only then their observations will be reproducible and valid. Pilot studies with a small number of healthy individuals should be initially performed to understand the maximum tolerable dose as information accrued from these studies can be of use in validating the preclinical observations.
ACKNOWLEDGMENTS The author RA is grateful to the director of INMAS, Delhi, for the support. Funding and support received from the Defence Research and Development Organization (DRDO), Government of India, are acknowledged. The author MSB is grateful to Rev. Fr. Patrick Rodrigus (Director), Rev. Fr. Denis D’Sa (Administrator), and Dr. Jaya Prakash Alva (Dean) of Father Muller Medical College for providing the necessary facilities and support. The authors declare no conflict of interest.
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REFERENCES Alam, M.S., Alam, M.A., Ahmad, S., Najmi, A.K., Asif, M., Jahangir, T., 2010. Protective effects of Punica granatum in experimentally-induced gastric ulcers. Toxicology Mechanisms and Methods 20, 572–578. Alanı´s, A.D., Calzada, F., Cervantes, J.A., Torres, J., Ceballos, G.M., 2005. Antibacterial properties of some plants used in Mexican traditional medicine for the treatment of gastrointestinal disorders. Journal of Ethnopharmacology 100 (1–2), 153–157. Al-Harbi, M.M., Qureshi, S., Raza, M., Ahmed, M.M., Afzal, M., Shah, A.H., 1997. Gastric antiulcer and cytoprotective effect of Commiphora molmol in rats. Journal of Ethnopharmacology 55 (2), 141–150. Ali, B.H., Blunden, G., Tanira, M.O., Nemmar, A., 2008. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food and Chemical Toxicology 46, 409–420. Al-Yahya, M.A., Rafatullah, S., Mossa, J.S., Ageel, A.M., Parmar, N.S., Tariq, M., 1989. Gastroprotective activity of ginger Zingiber officinale rosc, in albino rats. American Journal of Chinese Medicine 17, 51–56. Ammon, H.P., Wahl, M.A., 1991. Pharmacology of Curcuma longa. Planta Medica 57 (1), 1–7. Anthoni, C., Laukoetter, M.G., Rijcken, E., et al., 2006. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. American Journal of Physiology. Gastrointestinal and Liver Physiology 290, G1131–G1137. Arora, R. (Ed.), 2010. Herbal Drugs: A Cancer Chemopreventive and Therapeutic Perspective. Jaypee Brothers Medical Publishers (P) Ltd, New Delhi. Banerjee, D., Maity, B., Nag, S.K., Bandyopadhyay, S.K., Chattopadhyay, S., 2008. Healing potential of Picrorhiza kurroa (Scrofulariaceae) rhizomes against indomethacin-induced gastric ulceration: a mechanistic exploration. BMC Complementary and Alternative Medicine 8, 3. Bhatnagar, M., Sisodia, S.S., Bhatnagar, R., 2005. Antiulcer and antioxidant activity of Asparagus racemosus Willd and Withania somnifera Dunal in rats. Annals of the New York Academy of Sciences 1056, 261–278. Borrelli, F., Capasso, F., Capasso, R., et al., 2006. Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation. British Journal of Pharmacology 148 (4), 553–560. Castillo-Jua´rez, I., Gonza´lez, V., Jaime-Aguilar, H., et al., 2009. Anti-Helicobacter pylori activity of plants used in Mexican traditional medicine for gastrointestinal disorders. Journal of Ethnopharmacology 122 (2), 402–405. Chatterjee, T.K., Chakraborty, A., Pathak, M., Sengupta, G.C., 1992. Effects of plant extract Centella asiatica (Linn.) on cold restraint stress ulcer in rats. Indian Journal of Experimental Biology 30 (10), 889–891. Chrubasik, S., Pittler, M.H., Roufogalis, B.D., 2005. Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles. Phytomedicine 12, 684–701. Das, A.K., Mandal, S.C., Banerjee, S.K., et al., 1999. Studies on antidiarrhoeal activity of Punica granatum seed extract in rats. Journal of Ethnopharmacology 68 (1–3), 205–208. Dhuley, J.N., 2003. Investigation on the gastroprotective and antidiarrhoeal properties of Aegle marmelos unripe fruit extract. Hindustan Antibiotics Bulletin 45–46 (1–4), 41–46. Dos Reis, S.B., de Oliveira, C.C., Acedo, S.C., et al., 2009. Attenuation of colitis injury in rats using Garcinia cambogia extract. Phytotherapy Research 23, 324–329. Eamlamnam, K., Patumraj, S., Visedopas, N., Thong-Ngam, D., 2006. Effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing in rats. World Journal of Gastroenterology 12 (13), 2034–2039. El-Abhar, H.S., Hammad, L.N., Gawad, H.S., 2008. Modulating effects of ginger extract on rats with ulcerative colitis. Journal of Ethnopharmacology 118, 367–372. Feldman, M., Friedman, L.S., Sleisenger, M.H., 2006. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease, seventh ed. W.B. Saunders Company, Philadelphia, PA. Gupta, I., Parihar, A., Malhotra, P., et al., 2001. Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Medica 67, 391–395. Gupta, I., Parihar, A., Malhotra, P., et al., 1997. Effects of Boswellia serrata gum resin in patients with ulcerative colitis. European Journal of Medical Research 2, 37–43. Hanai, H., Sugimoto, K., 2009. Curcumin has bright prospects for the treatment of inflammatory bowel disease. Current Pharmaceutical Design 15, 2087–2094.
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Hills, J.M., Aaronson, P., 1991. The mechanism of action of peppermint oil on gastrointestinal smooth muscle. Gastroenterology 101, 55–65. Huang, C.H., Ku, C.Y., Jan, T.R., 2009. Diosgenin attenuates allergen-induced intestinal inflammation and IgE production in a murine model of food allergy. Planta Medica 75, 1300–1305. Ishita, C., Kaushik, B., Uday, B., Banerjee, R.K., 2004. Turmeric and curcumin: biological actions and medicinal applications. Current Science 87, 44–53. Langmead, L., Rampton, D.S., 2001. Herbal treatment in gastrointestinal and liver disease – benefits and angers. Alimentary Pharmacology and Therapeutics 15, 1239–1252. Latella, G., Sferra, R., Vetuschi, A., et al., 2008. Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 245-trinitrobenzene sulphonic acid. European Journal of Clinical Investigation 384, 10–20. Londonkar, R.L., Poddar, P.V., 2009. Studies on activity of various extracts of Mentha arvensis Linn against drug induced gastric ulcer in mammals. World Journal of Gastrointestinal Oncology 1 (1), 82–88. Mahady, G.B., Pendland, S.L., Yun, G.S., Lu, Z.Z., Stoia, A., 2003. Ginger (Zingiber officinale Roscoe) and the gingerols inhibit the growth of Cag Aþ strains of Helicobacter pylori. Anticancer Research 23, 3699–3702. Mahendran, P., Sabitha, K.E., Devi, C.S., 2002a. Prevention of HCl-ethanol induced gastric mucosal injury in rats by Garcinia cambogia extract and its possible mechanism of action. Indian Journal of Experimental Biology 40, 58–62. Mahendran, P., Vanisree, A.J., Shyamala Devi, C.S., 2002b. The antiulcer activity of Garcinia cambogia extract against indomethacin-induced gastric ulcer in rats. Phytotherapy Research 16 (1), 80–83. Nanjundaiah, S.M., Annaiah, H.N., Dharmesh, M.S., 2009. Gastroprotective effect of ginger rhizome (Zingiber officinale) extract: role of gallic acid and cinnamic acid in Hþ, Kþ-ATPase/H. Pylori inhibition and anti-oxidative mechanism. Evidence Based Complementary and Alternative Medicine 2011, 2011; 249487. Pandian, R.S., Anuradha, C.V., Viswanathan, P., 2002. Gastroprotective effect of fenugreek seeds (Trigonella foenum graecum) on experimental gastric ulcer in rats. Journal of Ethnopharmacology 81 (3), 393–397. Pittler, M.H., Ernst, E., 1998. Peppermint oil for irritable bowel syndrome: a critical review and metaanalysis. American Journal of Gastroenterology 93, 1131–1135. Sairam, K., Rao, C.V., Goel, R.K., 2001. Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats. Indian Journal of Experimental Biology 39 (2), 137–142. Saito, H., Imanishi, K., Okabe, S., 1989. Effects of aloe extracts, aloctin A, on gastric secretion and on experimental gastric lesions in rats. Yakugaku Zasshi 109 (5), 335–339. Savrikar, S.S., Dole, V., Ravishankar, B., Shukla, V.J., 2010. A comparative pharmacological investigation of three samples of ‘Guduchi ghrita’ for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats. International Journal of Ayurveda Research 1, 67–72. Singh, K., Jaggi, A.S., Singh, N., 2009. Exploring the ameliorative potential of Punica granatum in dextran sulfate sodium induced ulcerative colitis in mice. Phytotherapy Research 23, 1565–1574. Singh, S., Khajuria, A., Taneja, S.C., et al., 2008. The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats. Phytomedicine 15, 408–415. Yamada, T., Hoshino, M., Hayakawa, T., et al., 1997. Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats. American Journal of Physiology 273, G355–G364. Yamahara, J., Mochizuki, M., Rong, H.Q., Matsuda, H., Fujimura, H., 1988. The anti-ulcer effect in rats of ginger constituents. Journal of Ethnopharmacology 23, 299–304. Yusuf, S., Agunu, A., Diana, M., 2004. The effect of Aloe vera A. Berger (Liliaceae) on gastric acid secretion and acute gastric mucosal injury in rats. Journal of Ethnopharmacology 93 (1), 33–37.
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Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review R. Arora⁎,†, P. Malhotra†, S. Sundriyal†, H.S. Yashavanth‡, R.J. Pai‡, M.S. Baliga‡ ⁎
Chief Controller Research and Development (Life Sciences and International Cooperation), New Delhi, India Institute of Nuclear Medicine and Allied Sciences, Delhi, India Father Muller Medical College, Mangalore, India
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1. INTRODUCTION The gastrointestinal tract (GIT) is anatomically an extensive tubular tract extending from the mouth to the anus, with accessory organs such as the salivary glands, pancreas, and hepatobiliary system. The gut is in physical continuity and is compartmentalized by thick sphincters, which carry out their specialized function under the control of the neurohormonal system. The GIT performs the important function of assimilation, absorption of nutrients, and elimination of the waste, and its optimal functioning is very essential for the optimal health of the individual (Feldman et al., 2006). The GIT is a sensitive organ and may be affected by various factors, both endogenous and exogenous. Some of the mild ailments include dyspepsia, altered bowel habits, acid peptic disease, gastroesophageal reflux disease, lactose intolerance, celiac disease, microbial infection, and worm infestation; the severe ones include the inflammatory bowel diseases (IBDs), chronic diarrhea, and cancer (Feldman et al., 2006). A number of drugs are available for the treatment of various gastrointestinal ailments/ diseases. However, the clinical evaluation of these drugs has shown the incidence of relapses and side effects (Feldman et al., 2006; Table 19.1). This has necessitated the need for nontoxic drugs that are effective and devoid of side effects, and medicinal plants are being actively investigated, especially in the preclinical models of study.
2. HERBAL DRUGS IN GASTROINTESTINAL AILMENTS/DISEASES According to the World Health Organization, more than three-fourths of the world population still uses herbal preparations for various day-to-day ailments. Treatment for gastrointestinal disorders consists in the use of herbal supplements for symptomatic relief and improvement in the physiologic function of the GIT. Surveys of varying design and quality among the general population have shown that 8–50% of people in Bioactive Food as Dietary Interventions for Liver and Gastrointestinal Disease http://dx.doi.org/10.1016/B978-0-12-397154-8.00033-6
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Table 19.1 Side Effects of the Commonly Used Drugs to Treat Various Gastrointestinal Ailments and Diseases Diseases Common drugs Common side effects
Acid peptic disease and dyspepsia
Aluminum hydroxide Magnesium hydroxide Calcium carbonate Sodium bicarbonate H2 blockers
Constipation
PPIs Sucralfate Prostaglandins Cascara sagrada and senna
Diarrhea
Phenolphthalein Osmotic laxatives Bulk laxatives Emollient laxatives Loperamide
Antispasmodics IBD
Codeine and paregoric Dicyclomine Sulfasalazine Glucocorticoids Azathioprine and 6-mercaptopurine Methotrexate
Antiprotozoal
Metronidazole
Antihelminthics
Mebendazole Albendazole Pyrantel pamoate Ivermectin Fluoroquinolones (ciprofloxacin) Macrolides (erythromycin) Aminoglycosides (gentamicin) Cephalosporins (ceftriaxone) Aminopenicillins (amoxicillin) 5-Fluorouracil Cisplatin Irinotecan
Antibacterial
Anticancer drugs
Constipation Loose stools Milk-alkali syndrome Systemic alkalosis Gynecomastia, impotence (cimetidine), levels of creatinine, transferases Hypochlorhydria, carcinoid tumor Constipation Diarrhea, uterine bleeding Excessive purgation and melanotic pigmentation of the colonic mucosa Carcinogenicity CNS depression Intestinal obstruction Granulomatous fibrosis Abdominal cramps, paralytic ileus (in children) Addiction Urinary hesitancy, drowsiness Allergic reactions, hepatitis, pancreatitis, agranulocytosis Fluid retention, fat redistribution, hyperglycemia, osteonecrosis Pancreatitis, lymphoma Leucopenia, hepatic fibrosis, hypersensitivity pneumonitis Metallic taste, abdominal cramps, thrombophlebitis (IV route) Nausea, allergic reactions, teratogenic Alopecia, neutropenia on prolonged use Anorexia, raised plasma SGOT levels Pruritus, arthralgia Juvenile arthropathy, dizziness Hepatitis, arrhythmias, allergic reaction Ototoxicity, nephrotoxicity Hypersensitivity, nephrotoxicity Diarrhea, rashes Pancytopenia, toxic CNS effects Ototoxicity Diarrhea, neutropenia, and thrombocytopenia
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
Western Europe and the United States have used some form of complementary therapy (Arora, 2010). In developing countries, the usage is even more widespread. Well-conducted random telephone surveys in the United States showed that the use of complementary and alternative medicine rose from 34% in 1990 to 42% in 1997. The single most widely used modality in 1997 was herbal medicine, which showed a 380% increase from 7 years earlier (Langmead and Rampton, 2001). India has a rich tradition of using plants to treat various ailments, and the Indian traditional systems of medicine, Ayurveda, Siddha, and Unani, as well as the innumerable folk medicines, utilize plants to treat various ailments, including gastrointestinal ailments and diseases. This chapter collates the scientific observations of various investigators on the gastroprotective effects of some commonly used medicinal plants (Figure 19.1) on the mechanisms responsible for the protective effects.
2.1 Aegle marmelos Commonly known as bael, A. marmelos is a tree originally indigenous to India but is today found growing in Pakistan, Sri Lanka, and other Southeast Asian countries. In Ayurveda, bael is utilized for its ability to treat an assortment of diseases, including diarrhea, dysentery, and dyspeptic symptoms. Marmelosin, isolated from the bael plant, has been reported to have antihelminthic and antibacterial activity. Various other constituents Trigonella foenum-graecum Aegle marmelos
Withania somnifera
Boswellia serrata
Mentha arvensis
Zingiber officinalis
Curcuma longa
Garcinia cambogia
Aloe arborescens Tinospora cordifolia
Picrorhiza kurroa
Punica granatum
Commiphora molmol Centella asiatica
Figure 19.1 Plants with scientifically validated gastrointestinal protective effects.
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and the presence of tannin and other mucilaginous substances have been detected in the plant. Some researchers have also observed beneficial effects in luvangetin, a pyranocoumarin obtained from the seeds of the bael plant, in the treatment of gastric ulceration. Preclinical studies with rats have shown that the extract of unripe bael fruit (50 and 100 mg kg1, ip) was effective in reducing ethanol-induced gastric ulceration but ineffective in other models of ulcerogenesis (hypothermic restraint stress and indomethacin). The extract was also effective in inhibiting castor oil-induced diarrhea, intestinal transit, as well as the accumulation of intestinal fluids in mice (Dhuley, 2003).
2.2 Aloe vera or Aloe arborescens Aloe vera is a medicinal plant since centuries and is accredited to promote intestinal motility and relieve constipation. Studies have shown that oral intake of aloe vera for 4 weeks affords clinical respite in patients suffering from ulcerative colitis. The Aloe vera gel has been validated to protect against gastric ulceration (Eamlamnam et al., 2006). Preclinical studies have shown that the ethanolic extract of Aloe vera was effective in reducing the acute gastric mucosal lesions produced by 0.6 M HCl and the acid output in pylorusligated and lumen-perfuse rats. The extract decreased the secretion of acid (Yusuf et al., 2004). Additionally, aloctin A, a glycoprotein isolated from the leaves also inhibited the volume of gastric juice, acid, and pepsin output in pylorus-ligated rats. It was also effective in inhibiting the development of Shay ulcers and indomethacin-induced gastric lesions as well as in inhibiting water-immersion stress lesions induced in pylorus-ligated rats (Saito et al., 1989).
2.3 Boswellia serrata B. serrata is an important Indian medicinal plant, and studies have shown that boswellic acid was effective in various gastrointestinal ailments. Scientific studies have shown it to be effective in ameliorating 2,4,5-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats (Latella et al., 2008) and in patients with ulcerative colitis (Gupta et al., 1997, 2001). Additionally, studies have shown that the semisynthetic form of acetyl-11keto-b-boswellic acid, an active principle of B. serrata, also prevented dextran sodium sulfate (DSS)-induced experimental murine colitis as assessed by gross and histological observations (Anthoni et al., 2006). The gum resin extract is also reported to reduce the electrically, acetylcholine-, and barium chloride-induced contractions in the isolated guinea pig ileum and to inhibit the upper gastrointestinal transit in croton oil-treated mice as well as castor oil-induced diarrhea (Borrelli et al., 2006). Boswellic acids, the active compounds, are also reported to possess antiulcer effects in the pyloric ligation, ethanol/HCl, (acute and chronic) acetylsalicylic acid, indomethacin, and cold restraint stress models of study (Singh et al., 2008).
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
2.4 Centella asiatica C. asiatica, commonly known as brahmi, is a small herbaceous annual plant of the family Mackinlayaceae. It is a mild adaptogen, mildly antibacterial, antiviral, anti-inflammatory, antiulcerogenic, anxiolytic, and a cerebral tonic, a circulatory stimulant, a diuretic, nervine, and vulnerary. The extract of C. asiatica is reported to inhibit the gastric ulceration induced by cold and restraint stress, and the effect was comparable to that of famotidine (H2 antagonist; Chatterjee et al., 1992). The fresh juice of C. asiatica is reported to be effective against ethanol-, aspirin-, cold restraint stress-, and pyloric ligation-induced gastric ulcers in rats. The drug increased the gastric juice mucin secretion and increased the mucosal cell glycoproteins signifying increase in cellular mucus. It also decreased cell shedding indicating fortification of mucosal barrier (Sairam et al., 2001).
2.5 Commiphora molmol C. molmol, commonly known as guggal, guggul, or mukul myrrh tree, is a flowering plant of the family Burseraceae. It is found from Northern Africa to Central Asia but is most common in northern India. The tree exudes a yellowish resin called gum guggul or guggulu, which has a balsamic odor. Guggul gum is useful in the treatment of lipid disorders, acne vulgaris, arthritis, and obesity. Studies have shown that aqueous suspension of the oleogum resin of C. molmol (250, 500, and 1000 mg kg1) was effective in protecting the gastric mucosa against the ulcers caused by 80% ethanol, 25% NaCl, 0.2 M NaOH, indomethacin, and combined indomethacin–ethanol treatment. The protective effect observed was attributed to its effect on mucus production, increase in nucleic acid, and nonprotein sulfhydryl concentration, which appears to be mediated through its free radical-scavenging, thyroid-stimulating, and prostaglandin-inducing properties (Al-Harbi et al., 1997).
2.6 Curcuma longa Curcuma is native to tropical South Asia and is widely found in India as well. Curcumin (diferuloylmethane), the major active ingredient of turmeric, is derived from the dried roots of C. longa. Its chemical formula is 1,7-bis-(4-hydroxy-3-methoxyphenyl)1,6-heptadiene-3,5-dione. Studies have shown that it has antioxidant properties and provides symptomatic relief in patients with IBD. Curcumin has been shown to inhibit the growth of transformed cells and colon carcinogenesis at the initiation, promotion, and progression stages in carcinogen-induced rodent models (Ammon and Wahl, 1991; Ishita et al., 2004). Curcumin has been found to inhibit forestomach and colon carcinogenesis. The active principle in various extracts of turmeric and curcumin has been shown to produce antiulcerogenic activity in rats. Curcumin is also reported to prevent/reduce the ulcerative colitis in experimental models and in humans (Hanai and Sugimoto, 2009).
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2.7 Garcinia cambogia G. cambogia is a plant indigenous to India and parts of Southeast Asia. The fruits, which resemble miniature pumpkins, are of use as both dietary and medicinal agents. Animal studies have shown that the G. cambogia fruit extract (1 g kg1 body weight per day for 5, 10, or 15 days) protected the gastric mucosa against the damage induced by indomethacin (Mahendran et al., 2002a) and HCl–ethanol-induced (Mahendran et al., 2002b) gastric mucosal injury. G. cambogia decreased acidity and increased the mucosal defense in the gastric areas, decreased lipid peroxidation, increased the activity of antioxidant enzymes, altered levels of protein and glycoproteins in the ulcerated mucosa, and maintained the gastric juice at near normal levels (Mahendran et al., 2002a,b). Experiments have shown that the fruit extract inhibited the TNBS-induced colitis in rats by preventing the damage and decreasing myeloperoxidase (MPO) activity, and by the expression of COX-2 and iNOS to reduce the colonic levels of PGE2 and IL-1b, and to reduce DNA damage in the colonocytes (Dos Reis et al., 2009).
2.8 Mentha arvensis Peppermint (family: Lamiaceae) is a herbaceous rhizomatous perennial plant growing in moist habitats, including streamsides and drainage ditches. Being a hybrid, it is usually sterile, producing no seeds and reproducing only vegetatively, spreading by its rhizomes. Peppermint oil is one of the most commonly used over-the-counter remedies for gastrointestinal ailments (Pittler and Ernst, 1998). It prevents smooth muscle contractions and can be used for relief from abdominal pain associated with irritable bowel syndrome. Its antispasmodic action is achieved via influx of calcium ions across the cell membrane (Hills and Aaronson, 1991). It is therefore indicated in the treatment of abdominal pain and distension of functional dyspepsia/IBS, particularly in subjects with flatulence. On the other hand, it may have side effects such as heartburn, anal burning, and discomfort. Scientific studies have shown that the petroleum ether, chloroform, or aqueous extract (375 mg kg1 oral) was effective in preventing ibuprofen plus pyloric ligation-, 0.6 mol l1 HCl-, and 90% ethanol-induced gastric ulcerations in rats (Londonkar and Poddar, 2009). The methanolic extract is also observed to possess antibacterial effects on Helicobacter pylori in vitro (Castillo-Jua´rez et al., 2009).
2.9 Picrorhiza kurroa P. kurroa commonly known as kutki and belonging to the family Scrophulariaceae, is a herb native to the Himalayan regions of India, Pakistan, and Nepal. The roots and rhizomes are medicinally the most important parts and are in great demand in the various traditional and folk systems of medicine (Banerjee et al., 2008). The powder, decoction, infusion, confection, and alcoholic extract of the roots and rhizomes are useful in treating
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
various liver ailments: their anticholestatic effects are useful in treating dyspepsia, chronic diarrhea, and infection of the upper respiratory tract, and their antioxidant and immunemodulatory effects in treating fevers. Studies have shown that the methanolic extract of P. kurroa rhizomes was effective in reducing the indomethacin-induced gastric ulceration in mice by reducing oxidative stress; promoting mucin secretion and prostaglandin synthesis; and augmenting expressions of cyclooxygenase enzymes and growth factors (Banerjee et al., 2008).
2.10 Punica granatum P. granatum, commonly known as pomegranate, is an important medicinal plant. Studies have shown that the standardized aqueous methanolic extract of pomegranate (490 and 980 mg kg1 body weight) was effective in reducing alcohol-, indomethacin-, and aspirin-induced, and pylorus-ligated gastric ulcerations. Pomegranate extract also reduced the gastric volume and total acidity and increased the pH and mucus secretion in pylorus-ligated rats (Alam et al., 2010). The methanolic extract of the pomegranate seeds is also shown to possess antidiarrheal activity against castor oil-induced diarrhea and PGE2-induced enteropooling, and to reduce the gastrointestinal motility in charcoal meal test in rats (Das et al., 1999). The aqueous and methanolic extracts of pomegranate are also reported to be effective against Escherichia coli, Shigella sonnei, Shigella flexneri, and Salmonella sp. in vitro (Alanı´s et al., 2005). Additionally, Singh et al. (2009) observed that feeding Swiss albino mice with hydromethanolic extracts of the pomegranate flower and its ellagic acid-rich fraction (100 mg kg1 and 200 mg kg1, po) decreased the DSSinduced ulcerative colitis. The effect was comparable to sulfasalazine (100 mg kg1, po) and sodium cromoglicate (40 mg kg1, ip). Histopathological studies showed that the extracts reduced the degree of ulceration, levels of MPO, histamine, and lipid peroxides (Singh et al., 2009).
2.11 Tinospora cordifolia T. cordifolia commonly named guduchi is a herbaceous vine of the family Menispermaceae and is an important medicinal plant in Ayurveda for treating various ailments. It is an antispasmodic, analgesic, antipyretic, and anti-inflammatory agent. It is given for intermittent fevers and infective conditions such as typhoid, malaria, filariasis, and leprosy. It also has anthelmintic properties. It is prescribed for urinary disorders, skin diseases, and eye diseases. It is also used in gout and rheumatoid arthritis. It has cardiotonic, hematinic, expectorant, antiasthmatic, and aphrodisiac actions. Recently, Savrikar et al. (2010) have observed that the Ayurvedic preparation of T. cordifolia is effective in forced swimming-induced hypothermia and gastric ulceration.
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2.12 Trigonella foenum-graecum Commonly known as fenugreek, the seeds of the plants are of use as both culinary and medicinal agents in various traditional and folk systems of medicine. Studies have also shown that fenugreek seeds were effective in reducing ethanol-induced gastric ulcer and that they mediate their protective effects by their antisecretory action, increasing the mucosal glycoproteins and the antilipid peroxidative effects. Histopathological observations showed that the soluble gel fraction derived from the seeds was more effective than omeprazole in preventing lesion formation (Pandian et al., 2002). Pretreatment with diosgenin has also been shown to prevent the indomethacin-induced intestinal inflammation (Yamada et al., 1997) and to inhibit the ovalbumin-induced intestinal allergic responses; it suppressed intestinal inflammation, the occurrence of diarrhea, infiltration and degranulation of mast cells, and the presence of mucin-containing goblet cells in the duodenum in mice (Huang et al., 2009). Diosgenin also reduced the crypt depth of the intestine (Huang et al., 2009).
2.13 Withania somnifera W. somnifera, also known as ashwagandha in Hindi and as Indian ginseng and Winter cherry in English, is a plant of the Solanaceae family. In the Ayurvedic system of medicine, ashwagandha is considered beneficial in the treatment of many diseases. Preclinical studies have shown that the methanolic extract of the ashwagandha root (100 mg kg1 body weight per day orally for 15 days) was effective in reducing the indomethacin- and swim (restraint)-induced gastric ulcerations in rats and that the effects were comparable to those of the standard drug ranitidine. The extract reduced the ulcer index, volume of gastric secretion, free acidity, and total acidity. A significant increase in the total carbohydrate and total carbohydrate/protein ratio was also observed. The extract increased the antioxidant enzymes (superoxide dismutase, catalase) and ascorbic acid, and concomitantly decreased the levels of lipid peroxidation (Bhatnagar et al., 2005).
2.14 Zingiber officinale The rhizome of Z. officinale, commonly known as ginger, is an important spice and an integral part of several medicinal formulations in Ayurveda, Siddha, Unani, Sri Lankan, Greek, Roman, Asian, Indian, Mediterranean, and Arabic systems of medicines. In the various systems of medicine, ginger has been reported to possess carminative effects; it has been shown to decrease the pressure on the lower esophagus, to lessen intestinal cramping, to prevent dyspepsia, and to reduce flatulence and bloating (Ali et al., 2008; Chrubasik et al., 2005). Ginger is efficacious in preventing nausea and vomiting (Ali et al., 2008; Chrubasik et al., 2005). Multiple studies have clearly shown that whole ginger and some of its phytochemicals are potent gastroprotective agents in various standard experimental models such as the HCl/ethanol-, 80% ethanol-, 0.6 M HCl-,
Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
0.2 M NaOH-, and 25% NaCl-, indomethacin-, aspirin-, reserpine-, and hypothermic restraint-induced-ulcers; the swim stress-/ethanol stress-induced ulcers; and the pylorus ligation-induced gastric ulcerations in rats (Al-Yahya et al., 1989; Nanjundaiah et al., 2009; Yamahara et al., 1988). Studies by Mahady et al. (2003) have also shown that the methanol extract of ginger, the extract fractions, and the isolated constituents, 6-,8-,10-gingerol and 6-shogoal, inhibited the growth of the different strains of H. pylori in vitro with a minimum inhibitory concentration in the range of 6.25–50 mg ml1. Scientific studies by El-Abhar et al. (2008) have shown that pretreatment with ginger extract ameliorated the acetic acid-induced edematous inflammation in the colon. Together, all these observations clearly indicate the myriad uses of ginger in the prevention and treatment of various gastrointestinal ailments.
3. CONCLUSION Preclinical studies suggest that commonly used Indian medicinal plants such as A. marmelos, Aloe vera or Aloe arborescens, P. granatum, T. foenum-graecum, B. serrata, C. longa, G. cambogia, C. molmol, C. asiatica, P. kurroa, T. cordifolia, W. somnifera, and Z. officinale are effective in ameliorating/preventing various gastrointestinal ailments. Of these, A. marmelos, B. serrata, P. granatum, T. foenum-graecum, Z. officinale, C. longa, and G. cambogia are observed to be the most promising. However, for them to be of clinical/pharmaceutical use, detailed investigations, which will bridge the gaps in the existing knowledge of these plants, are required. The three main areas of lacunas are the incompleteness of the pharmacological studies, the lack of phytochemical validation, and the lack of human studies. Detailed studies with different and more robust preclinical models on the mechanistic aspects and the active principles are required. Additionally, the phytochemicals that are responsible for the observed pharmacological properties are known to be variable depending on the plant age, part, and geographical and seasonal conditions. Studies should be performed with well-characterized extracts with the knowledge of the levels of their different vital bioactive components as only then their observations will be reproducible and valid. Pilot studies with a small number of healthy individuals should be initially performed to understand the maximum tolerable dose as information accrued from these studies can be of use in validating the preclinical observations.
ACKNOWLEDGMENTS The author RA is grateful to the director of INMAS, Delhi, for the support. Funding and support received from the Defence Research and Development Organization (DRDO), Government of India, are acknowledged. The author MSB is grateful to Rev. Fr. Patrick Rodrigus (Director), Rev. Fr. Denis D’Sa (Administrator), and Dr. Jaya Prakash Alva (Dean) of Father Muller Medical College for providing the necessary facilities and support. The authors declare no conflict of interest.
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Medicinal Plants as Remedies for Gastrointestinal Ailments and Diseases: A Review
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