Gastric And Duodenal Antiulcer Activity Of Alkaloids: A Review

Peptic ulcer disease is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Numerous natural products have been evaluated as therapeutics for the treatment of a variety of diseases, including this one. These products usually derive from plant and animal sources that contain active constituents such as alkaloids, flavonoids, terpenoids, tannins and others. The alkaloids are natural nitrogen-containing secondary metabolites mostly derived from amino acids and found in about 20% of plants. There has been considerable pharmacological research into the antiulcer activity of these compounds. In this work we review the literature on alkaloids with antiulcer activity, which covers about sixty-one alkaloids, fifty-five of which have activity against this disease when induced in animals. © 2008 by the authors; licensee Molecular Diversity Preservation International.131231983223Yuan, Y., Padol, I.T., Hunt, R.H., Peptic ulcer disease today (2006) Nat. Clin. Pract. Gastroenterol. Hepatol, 3, pp. 80-89Tarnawski, A.S., Cellular and molecular mechanisms of gastrointestinal ulcer healing (2005) Digest. Dis. Sci, 50, pp. 24-33Wallace, J.L., Granger, D.N., The cellular and molecular basis of gastric mucosal defense (1996) FASEB J, 10, pp. 731-740Kaunitz, J.D., Akiba, Y., Gastroduodenal mucosal defense: Role of endogenous mediators (2004) Curr. Opin. Gastroenterol, 20, pp. 526-532Bandyopadhyay, D., Biswas, K., Bhattacharyya, M., Reiter, R.J., Banerjee, R.K., Gastric toxicity and mucosal ulceration induced by oxygen-derived reactive species: Protection by melatonin (2001) Curr. Mol. Med, 1, pp. 501-513Cechinel Filho, V., Yunes, R.A., Estratégias para obtenção de compostos farmacologicamente ativos a partir de plantas medicinais: Conceitos sobre modificação estrutural para otimização da atividade. (1998) Quim. Nova, 21, pp. 99-105Kaplan, M.A.C., Gottlieb, O.R., Busca racional de princípios ativos em plantas. (1990) Interciência, 15, pp. 26-29Elisabetsky, E., Costa-Campos, L., Medicinal plant genetic resources and international cooperation: The Brazilian perspective (1996) J. Ethnopharmacol, 51, pp. 111-119Secco, R.S., Produtos naturais: Alternativa segura? (1990) Cienc. Cult, 42, pp. 807-810Ziegler, J., Facchini, P.J., Alkaloid biosynthesis: Metabolism and trafficking (2008) Annu. Rev. Plant Biol, 59, pp. 735-769Henriques, A.T.Limberger, R.P.Kerber, V.A.Moreno, P.R.H. In: Farmacognosia: da planta ao medicamento, 5 ed.Simões, C. M. O. et al., Eds. Editoras of the Universidades Federais de Santa Catarina and Rio Grande do Sul: Porto Alegre/Florianópolis, Brazil, 2004Chapter 29, pp. 765-792Moura, M.D., Torres, A.R., Oliveira, R.A.G., Diniz, M.F.F.M., Barbosa-Filho, J.M., Natural products as inhibitors of models of mammary neoplasia (2001) Brit. J. Phytother, 5, pp. 124-145Moura, M.D., Silva, J.S., Oliveira, R.A.G., Diniz, M.F.F.M., Barbosa-Filho, J.M., Natural products reported as potential inhibitors of uterine cervical neoplasia (2002) Acta Farm. Bonaerense, 21, pp. 67-74Silva, J.S., Moura, M.D., Oliveira, R.A.G., Diniz, M.F.F.M., Barbosa-Filho, J.M., Natural product inhibitors of ovarian neoplasia (2003) Phytomedicine, 10, pp. 221-232Gonçalves, M.C.R., Moura, L.S.A., Rabelo, L.A., Barbosa-Filho, J.M., Cruz, H.M.M., Cruz, J., Natural products inhibitors of HMG CoA reductase (2000) Rev. Bras. Farm, 81, p. 6371Almeida, R.N., Navarro, D.S., Barbosa-Filho, J.M., Plants with central analgesic activity (2001) Phytomedicine, 8, pp. 310-322Pereira, J.V., Modesto-Filho, J., Agra, M.F., Barbosa-Filho, J.M., Plant and plant-derived compounds employed in prevention of the osteoporosis (2002) Acta Farm. Bonaer, 21, pp. 223-234Morais, L.C.S.L., Barbosa-Filho, J.M., Almeida, R.N., Plants and bioactive compounds for the treatment of Parkinson's disease (2003) Arq. Fitomed, 1, pp. 127-132Rocha, L.G., Almeida, J.R.G.S., Macedo, R.O., Barbosa-Filho, J.M., A review of natural products with antileishmanial activity (2005) Phytomedicine, 12, pp. 514-535Barbosa-Filho, J.M., Vasconcelos, T.H.C., Alencar, A.A., Batista, L.M., Oliveira, R.A.G., Guedes, D.N., Falcão, H.S., Modesto-Filho, J., Plants and their active constituents from South, Central, and North America with hypoglycemic activity (2005) Rev. Bras. Farmacogn, 15, pp. 392-413Falcão, H.S., Lima, I.O., Santos, V.L., Dantas, H.F., Diniz, M.F.F.M., Barbosa-Filho, J.M., Batista, L.M., Review of the plants with anti-inflammatory activity studied in Brazil (2005) Rev. Bras. Farmacogn, 15, pp. 381-391Barbosa-Filho, J.M., Piuvezam, M.R., Moura, M.D., Silva, M.S., Lima, K.V.B., Cunha, E.V.L., Fechine, I.M., Takemura, O.S., Anti-inflammatory activity of alkaloids: A twenty century review (2006) Rev. Bras. Farmacogn, 16, pp. 109-139Barbosa-Filho, J.M., Medeiros, K.C.P., Diniz, M.F.F.M., Batista, L.M., Athayde-Filho, P.F., Silva, M.S., Cunha, E.V.L., Quintans-Júnior, L.J., Natural products inhibitors of the enzyme acetylcholinesterase (2006) Rev. Bras. Farmacogn, 16, pp. 258-285Barbosa-Filho, J.M., Martins, V.K.M., Rabelo, L.A., Moura, M.D., Silva, M.S., Cunha, E.V.L., Souza, M.F.V., Medeiros, I.A., Natural products inhibitors of the angiotensin converting enzyme (ACE). A review between 1980-2000 (2006) Rev. Bras. Farmacogn, 16, pp. 421-446Amaral, F.M.M., Ribeiro, M.N.S., Barbosa-Filho, J.M., Reis, A.S., Nascimento, F.R.F., Macedo, R.O., Plants and chemical constituents with giardicidal activity (2006) Rev. Bras. Farmacogn, 16 (SUPPL.), pp. 696-720Barbosa-Filho, J.M., Nascimento-Júnior, F.A., Tomaz, A.C.A., Athayde-Filho, P.F., Silva, M.S., Cunha, E.V.L., Natural products with antileprotic activity (2007) Rev. Bras. Farmacogn, 17, pp. 141-148Falcão, H.S., Mariath, I.R., Diniz, M.F.F.M., Batista, L.M., Barbosa-Filho, J.M., Plants of the American continent with antiulcer activity (2008) Phytomedicine, 15, pp. 132-146Al-Shabanah, O.A., Islam, M.W., Al-Gharably, N.M., Al-Harbi, M.M., Effect of khatamines and their enantiomers on aspirin, indomethacin, phenylbutazone and reserpine induced gastric ulcers in rats (1993) Res Commun. Subst. Abuse, 14, pp. 81-94Sandor, V., Cuparencu, B., Analysis of the mechanism of the protective activity of some sympathomimetic amines in experimental ulcers (1977) Pharmacology, 15, pp. 208-217Hirano, H., Tokuhira, T., Yokoi, T., Shingu, T., Gastric mucous membrane-protective principles of Coptidis rhizoma (1997) Nat. Med, 51, pp. 516-518Yamahara, J., Behavioral pharmacology of berberine-type alkaloids. (1). Central depressive action of Coptidis rhizoma and its constituents (1976) Nippon Yakurigaku Zasshi, 72, pp. 899-908Sabir, M., Akhter, M.H., Bhide, N.K., Further studies on pharmacology of berberine (1978) Indian J. Physiol. Pharmacol, 22, pp. 9-23Tan, P.V., Nyasse, B., Enow-Orock, G.E., Wafo, P., Forcha, E.A., Prophylactic and healing properties of a new anti-ulcer compound from Enantia chlorantha in rats (2000) Phytomedicine, 7, pp. 291-296Tan, P.V., Nyasse, B., Dimo, T., Wafo, P., Akahkuh, B.T., Synergistic and potentiating effects of ranitidine and two new anti-ulcer compounds from Enantia chlorantha and Voacanga africana in experimental animal models (2002) Pharmazie, 57, pp. 409-412Hirano, H., Tokuhira, T., Yoshioka, Y., Yokoi, T., Shingu, T., Analysis of gastric mucosus membrane-protective compounds in Coptidis rhizoma (2000) Nat. Med, 54, pp. 209-212Hirano, H., Osawa, E., Yamaoka, Y., Yokoi, T., Gastric-mucous membrane protection activity of coptisine derivatives (2001) Biol. Pharm. Bull, 24, pp. 1277-1281Sakurai, T., Sugawara, H., Saito, K.I., Kano, Y., Effects of TDEYA from Atractylodes rhizome on experimental gastric ulcer (1995) Phytother. Res, 9, pp. 340-345Kubo, M., Nogami, M., Nishimura, M., Moriura, T., Arichi, S., Studies of crude drugs about its origin, process and quality. I. The preventive effects of chinese crude drug "zhu" on experimental stomach ulcer an its pharmacological evaluation (1) (1983) Yakugaku Zasshi, 103, pp. 442-448Zhang, J.F., Yan, C.D., Zhang, Y.Q., Gao, W.Z., Zhai, X.M., Effect of scopolia drugs on the gastric mucosal lesion in rats (1990) Acta Pharmacol. Sin, 25, pp. 90-94Robert, A., Nezamis, J.E., Lancaster, C., Duodenal ulcers produced in rats by propionitrile. Factors inhibiting and aggravating such ulcers (1975) Toxicol. Appl. Pharmacol, 31, pp. 201-207Wan, Y.J., Effect of anisodamine on gastric ulcer induced by restraint water-immersion in rats (1993) Clin. Gastroenterol, 3, pp. 154-158Wang, J.L., Effect of anisodamine on the reserpine-induced gastric mucosal lesion in rats (2000) Zhongguo Bingli Shengli Zazhi, 16, pp. 237-242Yong, D.G., Geng, B.Q., Gu, G.G., Zhong, F.M., Yu, W.H., Anti-ulcer effect of anisodamine in rats (1991) Acta Pharmacol. Sin, 12, pp. 522-525Fallone, C.A., Morris, G.P., Topical nicotine protects rat gastric mucosa against ASA-induced damage. A role for mucosal fluid secretion in cytoprotection (1995) Digest. Dis. Sci, 40, pp. 936-942Yamazaki, M., Arai, A., Suzuki, S., Takeuchi, T., Protective effects of matrine and oxymatrine on stress ulcer in relation to their effects on the central nervous system (1984) Yakugaku Zasshi, 104, pp. 293-301Yamazaki, M., Shirota, H., Application of experimental stress ulcer test in mice for the survey of neurotropic naturally occurring drug materials (1981) Shoyakugaku Zasshi, 35, pp. 96-102Yamazaki, M., Arai, A., Antiulcerogenic activity of oxymatrine (1985) J. Pharmacobiodyn, 8. , s-51Zhu, Z.P., Zhang, M.F., Shen, Y.Q., Antiulcer components of Sophora viciifolia alkaloids (1993) Tianran Chanwu Yanjiu Yu Kaifa, 5, pp. 26-29Yamazaki, M., The pharmacological studies on matrine and oxymatrine (2000) Yakugaku Zasshi, 120, pp. 1025-1033Annamalai, A.R., Manavalan, R., Effects of Trikatu and its individual components and piperine on gastrointestinal tract: Trikatu - a bioavailable enhancer (1990) Indian Drugs, 27, pp. 595-604Bai, Y.F., Xu, H., Protective action of piperine against experimental gastric ulcer (2000) Acta Pharmacol. Sin, 21, pp. 357-359Tramontana, M., Renzi, D., Panerai, C., Surrenti, C., Nappi, F., Abelli, L., Evangelista, S., Capsaicin-like effect of resiniferatoxin in the rat stomach (1994) Neuropeptides, 26, pp. 29-32Park, J.S., Choi, M.A., Kim, B.S., Han, I.S., Kurata, T., Yu, R., Capsaicin protects against ethanol-induced oxidative injury in the gastric mucosa of rats (2000) Life Sci, 67, pp. 3087-3093Watanabe, H., Watanabe, K., Shimadzu, M., Kikuchi, T., Liu, Z., Anti-ulcer effect of steroidal alkaloids extracted from Pachysandra terminalis (1986) Planta Med, 52, pp. 56-58Konturek, P.C., Konturek, S.J., Majka, J., Zembala, M., Hahn, E.G., Melatonin affords protection against gastric lesions induced by ischemia-reperfusion possibly due to its antioxidant and mucosal microcirculatory effects (1997) Eur. J. Pharmacol, 322, pp. 73-77Ozaki, Y., Pharmacological studies of indole alkaloids obtained from domestic plants Uncaria rhynchophylla Miq. and Amsonia elliptica Roem. et Schult (1989) Nippon Yakurigaku Zasshi, 94, pp. 17-26Omoto, T, Shinho, Y, Nakajima, K, Ishiwatari, H, Ito, H. Antiulcer alkaloids from Picrasma ailanthus. Jpn Kokai Tokkyo Koho 02004790, 1990Niiho, Y., Mitsunaga, K., Koike, K., Ohmoto, T., Studies on the gastric antiulcer components from the woods of Picrasma quassioides (Simaroubaceae) (1994) Nat. Med, 48, pp. 116-121Noldin, V.F., Martins, D.T.O., Marcello, C.M., Lima, J.C.S., Monache, F.D., Cechinel-Filho, V., Phytochemical and antiulcerogenic properties of rhizomes from Simaba ferruginea St. Hill. (Simaroubaceae) (2005) Z. Naturforsch. C, 60, pp. 701-706Toma, W., Trigo, J.R., Bensuaski de Paula, A.C., Souza Brito, A.R.M., Preventive activity of pyrrolizidine alkaloids from Senecio brasiliensis (Asteraceae) on gastric and duodenal induced ulcer on mice and rats (2004) J. Ethnopharmacol, 95, pp. 345-351Cicotti, I. Pharmaceutical composition for treating gastro-duodenal ulcers (1981), GB 2054373Istudor, V., Mantoiu, M., Badescu, I., Study on the preparation of an "instant" type product (Ulcovex) for gastric and duodenal ulcers. Part I. Chemical study of Calendulae flores product preparation of the "instant" type extract and determination of the control methodology (1981) Farmacia (Bucharest), 29, pp. 41-48Hikino, H., Kiso, Y., Ogata, M., Konno, C., Aisaka, K., Kubota, H., Hirose, N., Ishihara, T., Pharmacological actions of analogues of feruloylhistamine, an imidazole alkaloid of Ephedra roots (1984) Planta Med, 50, pp. 478-480Sinha, M., Sikdar, S., Dasgupta, S.R., Study of the effects of curcumin on 5-HT induced gastric lesions in guinea pigs (1975) Indian Med. Gaz, 15, p. 318Machova, J, Nosalova, V, Babulova, A. Pharmaceuticals for stomach ulcer treatment. Czech Patent 274070, 1992Al-Shabanah, O.A., Al-Gharably, N.A., Islam, M.W., Al-Harbi, M.M., Effect of cathinone, an active constituent of khat (Catha edulis Forsk) and amphetamine on experimental gastric ulcer and secretions (1992) Med. Sci. Res, 20, pp. 817-819Iwasa, J.Naruto, S.Ikeda, N.Sohji, Y. Salt of dehydrocorydaline. Can. Pat. CA 934547, 1974Watanabe, K., Goto, Y., Murakami, M., Mode of action of dehydrocorydaline on gastric acid secretion in rats (1974) Oyo Yakuri, 8, p. 1105Sohji, Y., Kawashima, K., Shimizu, M., Effect of dehydrocorydaline chloride on experimental gastric and duodenal ulcers (1974) Nippon Yakurigaku Zasshi, 70, pp. 425-437Nishioka, I., Takao, N., Nonaka, G., Iwasa, K., Corydamine and tetrahydrocorydamine derivatives. (1974), Jpn. Kokai Tokkyo Koho 49125399Nishioka, I., Takao, N., Nonaka, G., Iwasa, K.T., (1974), Jpn. Kokai Tokkyo Koho 49125398Chaumontet, M., Capt, M., Gold-Aubert, P., Comparative study of two anti-ulcerogenic drugs-glaziovine and sulpiride (1978) Arzneimittelforsch, 28, pp. 2119-2121Galeone, M., Cacioli, D., Moise, G., Gherardi, G., Quadro, G., Glaziovine as antiulcer: A double-blind short-term controlled clinical trial in comparison with cimetidine (1981) Curr. Ther. Res, 30, pp. 44-49Ishii, Y., Fujii, Y., Effects of several mild antiulcer agents on pylorus ligated rats (shay rats) (1974) Nippon Yakurigaku Zasshi, 70, p. 863Kang, J.Y., Teng, C.H., Wee, A., Chen, F.C., Effect of capsaicin and chilli on ethanol induced gastric mucosal injury in the rat (1995) Gut, 36, pp. 664-669Abdel Salam, O.M.E., Szolcsanyi, J., Mozsik, G., Capsaicin and its analogue resiniferatoxin inhibit gastric acid secretion in pylorus-ligated rats (1995) Pharmacol. Res, 31, pp. 341-345Abdel Salam, O.M.E., Mozsik, G., Szolcsanyi, J., Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats (1995) Pharmacol. Res, 32, pp. 209-215Kang, J.Y., Teng, C.H., Chen, F.C., Effect of capsaicin and cimetidine on the healing of acetic acid induced gastric ulceration in the rat (1996) Gut, 38, pp. 832-836Wan, J.L., Wang, C., Cui, S.Z., Effect of tetramethylpyrazine on gastric ulcer induced by restraint/water-immersion stress in rats (2000) Chung Ts'ao Yao, 31, pp. 115-117Yamahara, J., Konoshima, T., Sawada, T., Fujimura, H., Biologically active principles of crude drugs: Pharmacological actions of Swertia japonica extracts, swertiamarin and gentianine (1978) Yakugaku Zasshi, 98, pp. 1446-1451Hikino, H., Tamada, M., Yen, K.Y., Mallorepine, cyano-gamma-pyridone from Mallotus repandus (1978) Planta Med, 33, pp. 385-388Sun, Y.S., Ma, Z.S., Fan, Y.H., Wang, W.L., Yin, S.Y., Liu, C.K., Chen, W.Y., Deng, S.J., Chemical reformation of cuscohygrine (1975) K'o Hsueh T'ung Pao, 20, pp. 427-428Gorecki, P., Drozdzynska, M., Kedzia, B., Przybylska, D., Synthesis and biological activity of tropine alkaloids quaternary derivatives I. Tropine derivatives (1983) Herba Pol, 29, pp. 135-149Arai, A., Yamazaki, M., Study of antisecretory effect of oxymatrine, a constituent of Sophora flavescens (1987) J. Pharmacobiodyn, 10. , s-5