Phytochemistry Reviews

, Volume 11, Issue 4, pp 567–616 | Cite as

The therapeutic lead potential of metabolites obtained from natural sources for the treatment of peptic ulcer

  • Luiz Carlos Klein-Júnior
  • José Roberto Santin
  • Rivaldo Niero
  • Sérgio Faloni de Andrade
  • Valdir Cechinel-Filho
Article

Abstract

For over a century, ulcer has been a major cause of morbidity and mortality. Its treatment has progressed from vagotomy to proton pump inhibitors. However, the drugs used produce many adverse effects and are less effective than they ought to be. Therefore, there is a growing interest in alternative therapies and the use of natural products. This review emphasizes recent studies involving naturally occurring antiulcer metabolites, categorized according to their chemical structure. Both terrestrial and marine sources are included. More than a hundred and fifty different compounds are presented, and where possible, their main mechanisms of action are summarized. Considering that Helicobacter pylori is an important causal factor in the pathogenesis of ulcer disease, an overview of some natural compounds with anti-H. pylori activity is presented.

Keywords

Ulcer Secondary metabolites Gastroprotection 

Notes

Acknowledgments

The authors are grateful to CNPq, FAPESC, and ProPPEC/UNIVALI for their financial support. They also thank all the authors who have participated in the articles cited in the present work.

References

  1. Abdel-Salam OME, Szolcsányi J, Mózsik G (1997) Capsaicin and the stomach. A review of experimental and clinical data. J Physiol 91:151–171Google Scholar
  2. Abdul-Aziz KK (2011) Comparative evaluation of the anti-ulcer activity of curcumin and omeprazole during the acute phase of gastric ulcer. Food Nut Sci 2:628–640CrossRefGoogle Scholar
  3. Adhikary A, Yadav SK, Bandyopadhyay SK, Chattopadhyay S (2011) Epigallocatechin gallate accelerates healing of indomethacin-induced stomach ulcers in mice. Pharmacol Rep 63:527–536PubMedGoogle Scholar
  4. Aidong W, Zhipeng W, Taijun H, Yanyan J, Tingting Z, Yin W, Xuan G, Zhifu Y (2007) Analysis of sofalcone in human plasma by high performance liquid chromatography. J Chromatogr A 856:348–352Google Scholar
  5. Akagi M, Matsui N, Mochizuki S, Tasaka K (2001) Inhibitory effect of egualen sodium: a new stable derivative of azulene on histamine release from mast cell-like cells in the stomach. Pharmacology 63:203–209PubMedCrossRefGoogle Scholar
  6. Albinus M, Frisch G, Hennings G (1983) Histidine decarboxylase inhibition by O-methyl-3(+)-catechin and gastric acid secretion in the cat. Agents Actions 13:249–251PubMedCrossRefGoogle Scholar
  7. Al-Gharably NM, Islam MW, Al-Harbi MM, Al-Shabanah OA (1996) Canthinone [(R) (+)-α-aminopropiophenone]: a potent anti-gastric ulcer agent. Res Commun Alcohol Subst Abuse 17:165–184Google Scholar
  8. Almeida ABA, Melo PS, Hiruma-Lima CA, Gracioso JS, Carli L, Nunes DS, Haun M, Brito ARMS (2003) Antiulcerogenic effect and cytotoxic acttivity of semi-synthetic crotonin obtained from Croton cajucara Benth. Eur J Pharmacol 472:205–212CrossRefGoogle Scholar
  9. Almeida ABA, Miotto AM, Nunes DS, Spadari-Bratfisch RC, Brito ARMS (2002) Mechanism of antiulcerogenic activity of semi-synthetic crotonin obtained from Croton cajucara Benth. Rev Bras Farmacogn 12:105–110CrossRefGoogle Scholar
  10. Almeida ESS, Cechinel-Filho V, Niero R, Clasen BK, Balogun SO, Martins DTO (2011) Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. In animal models. J Ethnopharmacol 134:630–636CrossRefGoogle Scholar
  11. Alqasoumi S, Al-Sohaibani M, Al-Hwiriny T, Al-Yahya M, Rafatullah S (2009) Rocket “Eruca sativa”: a salad herb with potential gastric anti-ulcer activity. World J Gastroenterol 15:1958–1965PubMedCrossRefGoogle Scholar
  12. Amani ASA, Maitland DJ, Soliman GA (2006) Antiulcerogenic activity of Alhagi maurorum. Pharm Biol 44:292–296CrossRefGoogle Scholar
  13. Andrade SF, Antoniolli D, Comunello E, Cardoso LGV, Carvalho JCT, Bastos JK (2006) Antiulcerogenic activity of crude extract, fractions and populnoic acid isolated from Austroplenckia populnea (Celastraceae). Z Naturforsch 61c:329–333Google Scholar
  14. Arakawa T, Higuchi K, Fukuda T, Fujiwara Y, Kobayashi K, Kuroki T (1998) Prostaglandins in the stomach: an update. J Clin Gastroenterol 27:S1–S11PubMedCrossRefGoogle Scholar
  15. Arakawa T, Nakamura A, Yamada H, Nebiki H, Satoh H, Fukuda T, Kobayashi K (1988) Protection of gastric surface epithelial cells of rats by 16, 16-dimethyl prostaglandin E2 and sofalcone, a synthetic flavonoid derivative of sophoradin, against ethanol. Digestion 41:61–67PubMedCrossRefGoogle Scholar
  16. Arrieta J, Benitez J, Flores E, Castillo C, Navarrete A (2003) Purification of gastroprotective triterpenoids from the stem bark of Amphipterygium adstringens; role of prostaglandins, dulfhydryls, nitric oxide and capsaicin-senstive neurons. Planta Med 69:905–909PubMedCrossRefGoogle Scholar
  17. Arslan SO, Gelir E, Armutcu F, Coskun O, Gurel A, Sayan H, Celik IL (2005) The protective effect of thymoquinone on ethanol-induced acute gastric damage in the rat. Nutr Res 25:673–680CrossRefGoogle Scholar
  18. Asakuma Y, Kudo M, Matsui S, Okada M, Kawasaki M, Umehara Y, Ichikawa T, Kitai S (2009) Comparison of an ecabet sodium and proton pump inhibitor (PPI) combination therapy with PPI alone in the treatment of endoscopic submucosal dissection (ESD)-induced ulcers in early gastric cancer: prospective randomized study. Hepatogastroenterology 56:1270–1273PubMedGoogle Scholar
  19. Awaad AS, Mohamed NH, Maitland DJ, Soliman GA (2008) Anti-ulcerogenic activity of extract and some isolated flavonoids from Desmostachia bipinnata (L.) Stapf. Rec Nat Prod 2:76–82Google Scholar
  20. Barkun A, Leontiadis G (2010) Systematic review of the symptom burden, quality of life impairment and costs associated with peptic ulcer disease. Am J Med 123:358–366PubMedCrossRefGoogle Scholar
  21. Barros MP, Lemos M, Maistro EL, Leite MF, Sousa JPB, Bastos JK, Andrade SF (2008) Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis. J Ethnopharmacol 120:372–377PubMedCrossRefGoogle Scholar
  22. Barzaghi N, Gatti G, Crema F, Perucca E (1991) Protective effect of cyanidin (IdB 1027) against aspirin-induced fall in gastric transmucosal potential difference in normal subjects. Ital J Gastroenterol 23:249–252PubMedGoogle Scholar
  23. Bayir Y, Odabasoglu F, Cakir A, Aslan A, Suleyman H, Halici M, Kazaz C (2006) The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine 13:584–590PubMedCrossRefGoogle Scholar
  24. Bennett A, Melhuish PB, Stamford IF (1985) Carbenoxolone and deglycyrrhized liquorice have little or no effect on prostanoid synthesis by rat gastric mucosa ex vivo. Br J Pharmacol 86:693–695PubMedCrossRefGoogle Scholar
  25. Bezerra SB, Leal LKAM, Nogueira NAP, Campos AR (2009) Bisabolol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide, and KATP+ channels. J Med Food 12:1403–1406PubMedCrossRefGoogle Scholar
  26. Bhattacharya S, Banerjee D, Bauri AK, Chattopadhyay S, Bandyopadhyay SK (2007) Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action. World J Gastroenterol 13:3705–3713PubMedGoogle Scholar
  27. Bhounsule SA, D’Souza RS, Dhume VG (1994) Gastric cytoprotective effet of morphine is probably not mediated by mu-receptors. Arch Int Pharmacodyn Ther 328:99–105PubMedGoogle Scholar
  28. Bhounsule SA, D’Souza RS, Dhume VG (1992) Protective effect of morphine on ethanol-induced gastric lesions in rats: are ATP-dependent potassium channels involved? Arch Int Pharmacodyn Ther 318:116–123PubMedGoogle Scholar
  29. Biondo TMA, Tanae MM, Coletta ED, Lima-Landman MTR, Lapa AJ, Souccar C (2011) Antisecretory actions of Baccharis trimera (Less.) DC aqueous extract and isolated compounds: analysis of underlying mechanisms. J Ethnopharmacol 136:368–373PubMedCrossRefGoogle Scholar
  30. Brito RMS, Rodríguez JA, Hiruma-Lima CA, Haun M, Nunes DS (1998) Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara. Planta Med 64:126–129PubMedCrossRefGoogle Scholar
  31. Cechinel-Filho V, Meyre-Silva C, Niero R (2009) Chemical and pharmacological aspects of the genus Calophyllum. Chem Biodivers 6:313–327PubMedCrossRefGoogle Scholar
  32. Chan FKL, Leung WK (2002) Peptic-ulcer disease. Lancet 360:933–941PubMedCrossRefGoogle Scholar
  33. Chattopadhyay I, Bandyopadhyay U, Biswas K, Maity P, Banerjee RK (2006) Indomethacin inactivates gastric peroxidase to induce reative-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen. Free Rad Biol Med 40:1397–1408PubMedCrossRefGoogle Scholar
  34. Cho CH, Wu KK, Wu S, Wong TM, So WHL, Liu ESL, Chu KM, Shin VY, Ye YN, Wong BCY (2003) Morphine as a drug for stress ulcer prevention and healing in the stomach. Eur J Pharmacol 460:177–182PubMedCrossRefGoogle Scholar
  35. Choi E, Hwang H, Kim I, Nam T (2009) Protective effects of a polysaccharide from Hizikia fusiformis against ethanol toxicity in rats. Food Chem Toxicol 47:134–139PubMedCrossRefGoogle Scholar
  36. Choi J, Raghavendran HRB, Sung N, Kim J, Chun B, Ahn DH, Choi H, Kang K, Lee J (2010) Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem Biol Interact 183:249–254PubMedCrossRefGoogle Scholar
  37. Choi SM, Shin JH, Kang KK, Ahn BO, Yoo M (2007) Gastroprotective effects of DA-6034, a new flavonoid derivative, in various gastric mucosal damage models. Dig Dis Sci 52:3075–3080PubMedCrossRefGoogle Scholar
  38. Cipriani TR, Mellinger CG, de Souza LM, Baggio CH, Freitas CS, Marques MCA, Gorin PAJ, Sassaki GL, Iacomini M (2008) Acidic heteroxlans from medicinal plants and their anti-ulcer activity. Carbohydr Polym 74:274–278CrossRefGoogle Scholar
  39. Cipriani TR, Mellinger CG, de Souza LM, Baggio CH, Freitas CS, Marques MCA, Gorin PAJ, Sassaki GL, Iacomini M (2006) A polysaccharide from a tea (infusion) of Maytenus ilicifoila leaves with anti-ulcer protective effects. J Nat Prod 69:1018–1021PubMedCrossRefGoogle Scholar
  40. Cipriani TR, Mellinger CG, de Souza LM, Baggio CH, Freitas CS, Marques MCA, Gorin PAJ, Sassaki GL, Iacomini M (2009) Polygalacturonic acid: another anti-ulcer polysaccharide from the medicinal plant Maytenus ilicifolia. Carbohydr Polym 78:361–363CrossRefGoogle Scholar
  41. Coşkun Ö, Kanter M, Armutçu F, Çetin K, Kaybolmaz B, Yazgan Ö (2004) Protective effects of quercetin, a flavonoid antioxidant, in absolute ethanol-induced acute gastric ulcer. Eur J Gen Med 1:37–42Google Scholar
  42. Cristoni A, Malandrino S, Magistretti MJ (1989) Effect of a natural flavonoid on gastric mucosal barrier. Arzneimittelforschung 39:590–592PubMedGoogle Scholar
  43. Cryer B (2000) NSAID gastrointestinal toxicity. Curr Opin Gastroenterol 16:495–502PubMedCrossRefGoogle Scholar
  44. De Leo M, De Tommasi N, Sanogo R, D’Angelo V, Germano MP, Bisignano G, Braca A (2006) Triterpenoid saponins from Pteleopsis suberosas tem bark. Phytochemistry 67:2623–2629PubMedCrossRefGoogle Scholar
  45. De Olinda TM, Lemos TLG, Machado LL, Rao VS, Santos FA (2008) Quebrachitol-induced gastroprotection against acute gastric lesions: role of prostaglandins, nitric oxide and KATP+ channels. Phytomedicine 15:327–333PubMedCrossRefGoogle Scholar
  46. Debreceni A, Debreceni B, Mózsik G (1997) A study of the actions of naloxone and morphine on gastric acid secretion and gastric mucosal damage in the rat. J Physiol 91:189–197Google Scholar
  47. Del Tacca M, Bernardini C, Corsano E, Soldani G, Rozé C (1987) Effects of morphine on gastric ulceration, barrier muçus and acid secretion in pylorus-ligated rats. Pharmacology 35:174–180PubMedCrossRefGoogle Scholar
  48. Dembinska-Kiec A, Pallapies D, Simmet T, Peskar BM, Peskar BA (1991) Effect of carbenoxolone on the biological activity of nitric oxide: relation to gastroprotection. Br J Pharmacol 104:811–816PubMedCrossRefGoogle Scholar
  49. Derelanko MJ, Long JF (1981) Carbonoxolen sodium protects rat gastric mucosa against ethanol-induced necrosis. Proc Soc Exp Biol Med 166:394–397PubMedGoogle Scholar
  50. Donadel JO, Guerreiro E, María OA, Wendel G, Enriz DR, Giordano SO, Tonn EC (2005) Gastric cytoprotective activity of ilicic aldehyde: structure–activity relationships. Bioorg Med Chem Lett 15:3547–3550PubMedCrossRefGoogle Scholar
  51. Du A, Ma X, Zhang J, Zhou X, Li Y, Zhang Y, Qiao W (2010) The protective effect of capsaicin receptor-mediated genistein postconditioning on gastric ischemia–reperfusion injury in rats. Dig Dis Sci 55:3070–3077PubMedCrossRefGoogle Scholar
  52. El-Abhar HS, Abdallah DM, Saleh S (2003) Gastroprotective activity of Nigella sativa oil and its constituent, thymoquinone, against gastric mucosal injury induced by ischaemia/reperfusion in rats. J Ethnopharmacol 84:251–258PubMedCrossRefGoogle Scholar
  53. Ene MD, Clamp JR, Roberts CJ (1988) Effects of cimetidine and carbenoxolone on gastric mucus. Gut 29:636–641PubMedCrossRefGoogle Scholar
  54. Falcão HS, Leite JA, Barbosa-Filho JM, Athayde-Filho PF, Chaves MCO, Moura MD, Ferreira AL, Almeida ABA, Souza-Brito ARM, Diniz MFFM, Batista LM (2008) Gastric and duodenal antiulcer activity of alkaloids: a review. Molecules 13:3198–3223CrossRefGoogle Scholar
  55. Foglio MA, Dias PC, Antônio MA, Possenti A, Rodrigues RAF, Silva EF, Rehder VLG, Carvalho JE (2002) Antiulcerogenic activity of some sesquiterpene lactones isolated from Artemisia annua. Planta Med 68:515–518PubMedCrossRefGoogle Scholar
  56. Formica JV, Regelson W (1995) Food Chem Toxicol 33:1061–1080PubMedCrossRefGoogle Scholar
  57. Franco L, Manara P, Erbetti I, Velo GP (1993) Anti-ulcer activity of carbenoxolone and ISF 3401 on PGE2 release in rat gastric mucosa. Pharmacol Res 27:141–150PubMedCrossRefGoogle Scholar
  58. Fu HY, Yabe Y, Asahi K, Hayashi Y, Murata H, Eguchi H, Tsujii M, Tsuji S, Kawano S (2005) (2E, 6Z, 10E)-7-Hydroxymethyl-3, 11, 15-trimethyl-2, 6, 10, 14-hexadecatatraen-1-ol (plaunotol) increases cyclooxygenase-2 expression via nuclear factor κB and cyclic AMP response element in rat gastric epithelial cells. Eur J Pharmacol 524:38–43PubMedCrossRefGoogle Scholar
  59. Fujikawa T, Yamaguchi A, Morita I, Takeda H, Nishibe S (1996) Protective effect of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats. Biol Pharm Bull 19:1227–1230PubMedCrossRefGoogle Scholar
  60. Furukawa O, Kume E, Sugamoto S, Kawauchi S, Takeuchi K (2000) Effect of ecabet disodium, a novel locally-acting antiulcer drug, on epithelial restitution following injury by hypertonic NaCl in bullfrog stomach in vitro. Digestion 62:116–125PubMedCrossRefGoogle Scholar
  61. Gálvez J, Sánchez de Medina F, Jiménez J, Zarzuelo A (2001) Effects of flavonoids on gastrointestinal disorders. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 25. Elsevier, Amsterdam, pp 607–649Google Scholar
  62. Ganguli PC, Mohamed SD (1980) Long-term therapy with carbenoxolone in the prevention of recurrence of gastric ulcer. Natural history and evolution of important side-effects and measures to avoid them. Scand J Gastroenterol Suppl 65:63–71PubMedGoogle Scholar
  63. Giordano OS, Guerreiro E, Pestchanker MJ, Guzmán JA, Pastor D, Guardia T (1990) The gastric cytoprotective effect of several sesquiterpene lactones. J Nat Prod 53:803–809PubMedCrossRefGoogle Scholar
  64. Glavin GB, Kernan K, Hnatowich MR, Labella FS (1986) Effects of morphine and naloxone on stress ulcer formation and gastric acid secretion. Eur J Pharmacol 124:121–127PubMedCrossRefGoogle Scholar
  65. Goel RK, Maiti RN, Manickam M, Ray AB (1997) Antiulcer activity of naturally occurring pyrano-coumarin and isocoumarins and their effect on prostanoid synthesis using human colonic mucosa. Indian J Exp Biol 35:1080–1083PubMedGoogle Scholar
  66. Goel RK, Pathak NK, Biswas M, Pandey VB, Sanyal AK (1987) Effect of lapachol, a naphtoquinone isolated from Tectona grandis, on experimental peptic ulcer and gastric secretion. J Pharm Pharmacol 39:138–140PubMedCrossRefGoogle Scholar
  67. González-Segovia R, Quintanar JL, Salinas E, Ceballos-Salazar R, Aviles-Jiménez F, Torres-López J (2008) Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol 43:441–447PubMedCrossRefGoogle Scholar
  68. Granger DN, Kubes P (1994) The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 55:662–675PubMedGoogle Scholar
  69. Green AP, Lander JE, Turner DH (1981) The effect of stress and indomethacin, carbenoxolone, salbutamol, metiamide, zolimidine and CF 19415 on rat gastric mucus. J Pharm Pharmacol 33:348–352PubMedCrossRefGoogle Scholar
  70. Green CE, Pearson DN, Christensen NB, Simon SI (2003) Topographic requirements and dynamics of signaling via l-selectin on neutrophils. Am J Physiol Cell Physiol 284:C705–C717PubMedGoogle Scholar
  71. Guardia T, Guzmán JA (1994) Mucus synthesis and sulfhydryl group in cytoprotection mediated by dehydroleucodine, a sesquiterpene lactone. J Nat Prod 57:507–509PubMedCrossRefGoogle Scholar
  72. Guedes MM, Carvalho ACS, Lima AF, Lira SRS, Queiroz SS, Silveira ER, Santos FA, Rao VSN (2008) Gastroprotective mechanisms of centipedic acid, a natural diterpene from Egletes viscose Less. Biol Pharm Bull 31:1351–1355PubMedCrossRefGoogle Scholar
  73. Guedes MM, Cunha AN, Silveira ER, Rao VSN (2002) Antinociceptive and gastroprotective effects of diterpenes from the flower buds of Egletes viscosa. Planta Med 68:1044–1046PubMedCrossRefGoogle Scholar
  74. Gurbuz I, Erdemoglu N, Yesilada E, Sener B (2004) Anti-ulcerogenic lignans from Taxus baccata L. Z Naturforsch 59c:233–236Google Scholar
  75. Gürbüz I, Yesilada E, Ito S (2009) An anti-ulcerogenic flavonol diglucoside from Equisetum palustre L. J Ethnopharmacol 121:360–365PubMedCrossRefGoogle Scholar
  76. Gürbüz I, Yesilada E (2007) Evaluation of the anti-ulcerogenic effect of sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis by using various in vivo and biochemical techniques. J Ethnopharmacol 112:284–291PubMedCrossRefGoogle Scholar
  77. Guslandi M, Cambieli M, Bierti L, Tittobello A (1980) Effect of carbenoxolone and cimetidine on gastric mucin. Clin Ther 3:40–42PubMedGoogle Scholar
  78. Guslandi M (1987) Effects of ethanol on the gastric mucosa. Dig Dis 5:21–32PubMedCrossRefGoogle Scholar
  79. Gyires K (1990) Morphine inhibits the ethanol-induced gastric damage in rats. Arch Int Pharmacodyn Ther 306:170–181PubMedGoogle Scholar
  80. Gyires K (1994) The role of endogenous nitric oxide in the gastriprotective action of morphine. Eur J Pharmacol 255:33–37PubMedCrossRefGoogle Scholar
  81. Hagel J, Demling L, Croft DN (1977) Gastric epithelial cell turnover, mucus production, and healing of gastric ulcers with carbenoxolone. Gut 18:817–820PubMedCrossRefGoogle Scholar
  82. Han SB, Jang MS, Lee HJ, Lee Y, Yu C, Lee KR, Kim H (2005) Simultaneous characterization of sofalcone and its metabolite in humana plasma by liquid chromatography–tandem mass spectrometry. Bull Korean Chem Soc 26:729–734CrossRefGoogle Scholar
  83. Higuchi K, Watanabe T, Tanigawa T, Tominaga K, Fujiwara Y, Arakawa T (2010) Sofalcone, a gastroprotective drug, promotes gastric ulcer healing following eradication therapy for Helicobacter pylori: a randomized controlled comparative trial with cimetidine, an H2-receptor antagonist. J Gastroenterol Hepatol 25:S155–S160PubMedCrossRefGoogle Scholar
  84. Hilton D, Iman N, Burke GJ, Moore A, O’Mara G, Signorini D, Lyons D, Banerjee AK, Clinch D (2001) Absence of abdominal pain in older persons with endoscopic ulcers: a prospective study. Am J Gastroenterol 96:380–384PubMedCrossRefGoogle Scholar
  85. Hiruma-Lima CA, Batista LM, Almeida ABA, Magri LP, Santos LC, Vilegas W, Brito ARMS (2009) Antiulcerogenic action of ethanolic extract of the resin from Virola surinamensis Warb. (Myristicaceae). J Ethnopharmacol 122:406–409PubMedCrossRefGoogle Scholar
  86. Hiruma-Lima CA, Spadari-Bratfisch RC, Grassi-Kassisse DM, Brito ARMS (1999) Antiulcerogenic mechanisms of dehydrocrotonin, a diterpene lactone obtained from Croton cajucara. Planta Med 65:325–330PubMedCrossRefGoogle Scholar
  87. Hiruma-Lima CA, Toma W, Gracioso JS, Almeida ABA, Batista LM, Magri L, Paula ACB, Soares FR, Nunes DS, Brito ARMS (2002) Natural trans-crotonin: the antiulcerogenic effect of another diterpene isolated from the bark of Croton cajucara Benth. Biol Pharm Bull 25:452–456PubMedCrossRefGoogle Scholar
  88. Ho MM, Dai S, Ogle CW (1984) Decreased acid secretion and gastric lesions production by morphine in rats. Eur J Pharmacol 102:117–121PubMedCrossRefGoogle Scholar
  89. Hussain T, Verma AR, Vijayakumar M, Sharma A, Mathela CS, Rao CV (2009) Rutin, a natural flavonoid, protects against gastric mucosal damage in experimental animals. Asian J Trad Med 4:188–197Google Scholar
  90. Hwang H, Kwon M, Kim I, Nam T (2008) The effect of polysaccharide extracted from the marine alga Capsosiphon fulvescens on ethanol administration. Food Chem Toxicol 46:2653–2657PubMedCrossRefGoogle Scholar
  91. Ishikawa T, Donatini SR, Diaz IE, Yoshida M, Bacchi EM, Kato ET (2008) Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats. J Ethnopharmacol 13:527–529CrossRefGoogle Scholar
  92. Isobe Y, Hirose H, Muramatsu M, Aihara H (1985) Cytoprotective effect of sofalcone in the rat gastric mucosa. Arzneimittelforschung 35:138–141PubMedGoogle Scholar
  93. Ito Y, Nakamura S, Onoda Y, Sugawara Y, Takaiti O (1993) Effects of the new anti-ulcer drug ecabet sodium (TA-2711) on pepsin activity. II. Interaction with substrate protein. Jpn J Pharmacol 62:169–174PubMedCrossRefGoogle Scholar
  94. Jainu M, Devi CS (2006) Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental ulcer models: possible mechanism for the inhibition of acid formation. J Ethnopharmacol 104:156–163PubMedCrossRefGoogle Scholar
  95. Jainu M, Mohan KV (2008) Protective role of ascorbic acid isolated from Cissus quadrangularis on NSAID induced toxicity through immunomodulating response and growth factors expression. Int Immunopharmacol 8:1721–1727PubMedCrossRefGoogle Scholar
  96. Jayaraj AP, Lewin MR, Tovey FI, Kitler ME, Clark CG (1988) The protective effect of meciadanol (O-methyl-3(+)-catechin) on experimental ulceration. Eur J Pharmacol 147:262–271CrossRefGoogle Scholar
  97. Jeong CS, Hyun JE, Kim YS (2003) Ginsenoside Rb1: the anti-ulcer constituent from the head of Panax ginseng. Arch Pharm Res 26:906–911PubMedCrossRefGoogle Scholar
  98. Kannappan S, Palanisamy N, Anuradha CV (2010) Suppression of hepatic oxidative events and regulation of eNOS expression in the liver by naringenin in fructose-administered rats. Eur J Pharmacol 645:177–184PubMedCrossRefGoogle Scholar
  99. Kanter M, Coskun O, Uysal H (2006) The antioxidative and antihistaminic effect of Nigella sativa and its major constituent, thymoquinone on ethanol-induced gastric mucosal damage. Arch Toxicol 80:217–224PubMedCrossRefGoogle Scholar
  100. Kanter M, Demir H, Karakaya C, Ozbek H (2005) Gastroprotective activity of Nigella sativa L oil and its constituent, thymoquinone against acute alcohol-induced gastric mucosal injury in rats. World J Gastroenterol 11:6662–6666PubMedGoogle Scholar
  101. Kasinathan C, Rizwan M, Slomiany A, Slomiany BL (1994) Effect of sofalcone on tyrosylprotein sulfotransferase. Gen Pharmacol 25:1017–1020PubMedCrossRefGoogle Scholar
  102. Katagiri F, Inoue S, Sato Y, Itoh H, Takeyama M (2005) Ecabet sodium raises plasma levels of calcitonin generelated peptide and substance P in healthy humans. J Pharm Pharmacol 57:799–805PubMedCrossRefGoogle Scholar
  103. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA (2002) Recent patterns of medication use in the ambulatory adult population of the United States: the Slone survey. JAMA 287:337–344PubMedCrossRefGoogle Scholar
  104. Kawase M, Motohashi N (2004) Plant-derived leading compounds for eradication of Helicobacter pylori. Curr Med Chem 3:89–100Google Scholar
  105. Khennouf S, Benabdallah H, Gharzouli K, Amira S, Ito H, Kim T, Yoshida T, Gharzouli A (2003) Effect of tannins from Quercus suber and Quercus coccifera leaves on ethanol-induced gastric lesions in mice. J Agric Food Chem 51:1469–1473PubMedCrossRefGoogle Scholar
  106. Kim H, Jang MS, Lee J, Pyo D, Yoon H, Lee HJ, Lee KR (2004) High-throughput analysis of sofalcone in human plasma by use of automated 96-well protein precipitation and LC-MS-MS. Chromatographia 60:335–339Google Scholar
  107. Kinoshita M, Endo M, Yasoshima A, Saito N, Yamasaki K, Chishima S, Narita H (1999) Ecabet sodium, a novel locally-acting anti-ulcer agent, protects the integrity of the gastric mucosal gel layer from pepsin-induced disruption in the rat. Aliment Pharmacol Ther 13:687–694PubMedCrossRefGoogle Scholar
  108. Kinoshita M, Iwasaki H, Yasoshima A, Tamaki H (1993) Effects of ecabet sodium (TA-2711), a new antiulcer agent, on gastrointestinal mucosal prostanoid production and morphology in rats. Biol Pharm Bull 16:1220–1225PubMedCrossRefGoogle Scholar
  109. Kinoshita M, Kume E, Tamaki H (1995) Roles of prostaglandins, nitric oxide and the capsaicin-sensitive sensory nerves in gastroprotection produced by ecabet sodium. J Pharmacol Exp Ther 275:494–501PubMedGoogle Scholar
  110. Kinoshita M, Tamaki H (1997) Possible mechanism of increase in gastric mucosal PGE2 and PGI2 generation induced by ecabet sodium, a novel gastroprotective agent. Dig Dis Sci 42:83–90PubMedCrossRefGoogle Scholar
  111. Kitazawa E, Ogiso A, Takahashi S, Sato A, Kurabayahi M, Kuwano H, Hata T, Tamura C (1979) Plaunotol A and B, new anti-ulcer diterpenelactones from Croton sublyratus. Tetrahedron Lett 13:1117–1120CrossRefGoogle Scholar
  112. Klein-Júnior LC, Gandolfi RB, Santin JR, Lemos M, Cechinel-Filho V, Andrade SF (2010) Antiulcerogenic activity of extract, fractions, and some compounds obtained from Polygala cyparissias St. Hillaire & Moquin (Polygalaceae). Naunyn-Schmiedeberg’s Arch Pharmacol 381:121–126CrossRefGoogle Scholar
  113. Klopell FC, Lemos M, Sousa JPB, Comunello E, Maistro EL, Bastos JK, Andrade SF (2007) Nerolidol, an antiulcer constituent from the essential oil of Baccharis dracunculifolia DC (Asteraceae). Z Naturforsch 62c:537–542Google Scholar
  114. Kobayashi K, Arakawa T, Nakamura A, Nakamura H (1990) Protective effect of sofalcone and 16, 16-dimethyl-PGE2 on isolated rat gastric cells. J Clin Gastroenterol 12:S177–S180PubMedCrossRefGoogle Scholar
  115. Kobayashi K, Higuchi K, Arakawa T, Matsumoto T, Nagura H (1992) Effect of sofalcone on localization of 15-hydroxyprostaglandin dehydrogenase, an enzyme that metabolizes prostaglandin E2, in rat gastric mucosa: an immunohistochemical study. J Clin Gastroenterol 14:S39–S42PubMedCrossRefGoogle Scholar
  116. Konturek SJ, Radecki T, Brzozowski T, Drozdowicz D, Piastucki I, Muramatsu M, Tanaka M, Aihara H (1986a) Antiulcer and gastroprotective effects of solon, a synthetic flavonoid derivative of sophoradin. Role of endogenous prostaglandins. Eur J Pharmacol 17:185–192CrossRefGoogle Scholar
  117. Konturek JS, Kitler ME, Brzozowski T, Radecki T (1986b) Gastric protection by meciadanol—a new synthetic flavonoid-inhibiting histidine decarboxylase. Dig Dis Sci 31:847–852PubMedCrossRefGoogle Scholar
  118. Konturek SJ, Mrzozowski T, Drozdowicz D, Pawlik W, Sendur R (1987) Gastroprotective and ulcer healing effects of solon, a synthetic flavonoid derivative of sophoradin. Hepatogastroenterology 34:164–170PubMedGoogle Scholar
  119. Koo MWL, Ogle CW, Cho CH (1986) Effects of verapamol, carbenoxolone and N-acetylcysteine on gastric wall mucus and ulceration in stressed rats. Pharmacology 32:326–334PubMedCrossRefGoogle Scholar
  120. Kubecova M, Kolostova K, Pinterova D, Kacprzak G, Bobek V (2011) Cimetidine: an anticancer drug? Eur J Pharm Sci 18:439–444CrossRefGoogle Scholar
  121. Kyogoku K, Hatayama K, Yokomori S, Saziki R, Nakane S, Sasajima M, Sawada J, Ohzeki M, Tanaka I (1979) Anti-ulcer effect of isoprenyl flavonoids. II. Synthesis and anti-ulcer activity of new chalcones related to sophoradin. Chem Pharm Bull 27:2943–2953PubMedCrossRefGoogle Scholar
  122. La Brooy SJ, Taylor RH, Hunt RH, Golding PL, Laidlaw JM, Chapman RG, Pounder RE, Vincent SH, Colin-Jones DG, Milton-Thompson GJ, Misiewicz JJ (1979) Controlled comparison of cimetidine and carbenoxolone sodium in gastric ulcer. Br Med J 1:1308–1309PubMedCrossRefGoogle Scholar
  123. Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dharmani P, Mishra V, Palit G (2010) Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. Phytomedicine 17:569–574PubMedCrossRefGoogle Scholar
  124. Layton D, Souverein PC, Heerdink ER, Shakir SAW, Antoine ACG (2008) Evaluation of risk profiles for gastrointestinal and cardiovascular adverse effects in nonselective NSAID and COX-2 inhibitor users: a cohort study using pharmacy dispensing data in The Netherlands. Drug Saf 31:143–158PubMedCrossRefGoogle Scholar
  125. Lee EB, Kim OJ, Kang SS, Jeong C (2005) Araloside A, an antiulcer constituent from the root bark of Aralia elata. Biol Pharm Bull 28:523–526PubMedCrossRefGoogle Scholar
  126. Lee J, Lee S, Kim YS, Jeong CS (2009) Protective effects of neohesperidin and pncirin isolated from the fruits of Poncirus trifoliate on potential gastric disease. Phytother Res 23:1748–1753PubMedCrossRefGoogle Scholar
  127. Lee K, Yeo M, Choue J, Jin J, Park SJ, Cheong J, Lee KJ, Kim J, Hahm K (2004) Protective mechanism of epigallocatechin-3-gallate against Helicobacter pylori-induced gastric epithelial cytotoxicity via the blockage of TLR-4 signaling. Helicobacter 9:632–642PubMedCrossRefGoogle Scholar
  128. Lehtola J, Karvonen AL, Tunturi-Hihnala H (1978) Double-blind study of carbenoxolone in gastric ulcer and erosions. Ann Clin Res 10:19–23PubMedGoogle Scholar
  129. Li A, Xu H, Zhao B, Chang H, Rhee H (2008) Gastroprotective effect of cyaniding 3-glucoside on ethanol-induced gastric lesions in rats. Alcohol 42:683–687PubMedCrossRefGoogle Scholar
  130. Li Y, Zhang J, Zhang Y, Ma X (2009) The protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells. Acta Pharmacol Sin 30:576–581PubMedCrossRefGoogle Scholar
  131. Lira SR, Rao VS, Carvalho AC, Guedes MM, de Morais TC, de Souza AL, Trevisan MT, Lima AF, Chaves MH, Santos FA (2009) Gastroprotective effect of lupeol on ethanol-induced gastric damage and the underlying mechanism. Inflammopharmacology 17:221–228PubMedCrossRefGoogle Scholar
  132. Liu J, Du J, Fan L, Liu X, Gu L, Ge Y (2008a) Effects of quercetin on hyper-proliferation of gastric mucosal cells in rats treated with chronic oral ethanol through the reactive oxygen species-nitric oxide pathway. World J Gastroenterol 14:3242–3248PubMedCrossRefGoogle Scholar
  133. Liu Y, Zhou Y, Li D, Wang L, Hu G, Peng J, Li Y (2008b) Reduction of asymmetric dimethlarginine in the protective effects of rutaecarpine on gastric mucosal injury. Can J Physiol Pharmacol 86:675–681PubMedCrossRefGoogle Scholar
  134. Lu CL, Chang SS, Wang SS, Chang FY, Lee SD (2004) Silent peptic ulcer disease: frequency, factors leading to “silence,” and implications regarding the pathogenesis of visceral symptoms. Gastrointest Endosc 60:34–38PubMedCrossRefGoogle Scholar
  135. Maciel MAM, Pinto AC, Arruda AC, Pamplona SGSR, Vanderlinde FA, Lapa AJ, Echevarria A, Grynberg NF, Côlus IMS, Farias RAF, Costa AML, Rao VSN (2000) Ethnopharmacology, phytochemistry and pharmacology: a successful combination in the study of Croton cajucara. J Ethnopharmacol 70:41–55PubMedCrossRefGoogle Scholar
  136. Madhukar M, Sawraj S, Sharma PD (2010) Design, synthesis and evaluation of mutual prodrug of 4-biphenulacetic acid and quercetin tetramethol ether (BPA-QTME) as gastrosparing NSAID. Eur J Med Chem 45:2591–2596PubMedCrossRefGoogle Scholar
  137. Mahattanadul S, Nakamura T, Panichayupakaranant P, Phdoongsombut N, Tungsinmunkong K, Bouking P (2009) Comparative antiulcer effect of bisdemethoxycurcumin and curcumin in a gastric ulcer model system. Phytomedicine 16:342–351PubMedCrossRefGoogle Scholar
  138. Mahattanadul S, Reanmongkol W, Yano S, Panichayupakaranant P, Phdoongsombut N, Tungsinmunkong K (2006) Preventive and curative effects of curcumin on the development of gastric inflammatory diseases in rats. J Nat Med 60:191–197CrossRefGoogle Scholar
  139. Mahattanadul S, Ridtitid W, Nima S, Phdoongsombut N, Ratanasuwon P, Kasiwong S (2011) Effects of Morinda citrifolia aqueous fruit extract and its biomarker scopoletin on reflux esophagitis and gastric ulcer in rats. J Ethnopharmacol 134:243–250PubMedCrossRefGoogle Scholar
  140. Maity B, Chattopadhyay S (2008) Natural antiulcerogenic agents: an overview. Curr Bioact Compd 4:225–244CrossRefGoogle Scholar
  141. Marrotta F, Tajiri H, Safran P, Fesce E, Ideo G (1999) Ethanol-related gastric mucosal damage: evidence of a free radical-mediated mechanism and beneficial effect of oral supplementation with bionormalizer, a novel natural antioxidant. Digestion 60:538–543CrossRefGoogle Scholar
  142. Martín MJ, Alarcón de La Lastra C, Motilva V, La Casa C (2000) Antiulcer and gastroprotectice activity of flavonic compounds: mechanisms involved. In: Atta-ur-Rahman (ed) Studies in natural products chemistry, vol 22. Elsevier, Amsterdam, pp 419–456Google Scholar
  143. Massignani JJ, Lemos M, Maistro EL, Schaphauser HP, Jorge RF, Sousa JPB, Bastos JK, Andrade SF (2009) Antiulcerogenic activity of the essential oil of Baccharis dracunculifolia on different experimental models in rats. Phytoter Res 23:1355–1360CrossRefGoogle Scholar
  144. Matsuda H, Li Y, Yoshikawa M (1999) Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulfhydryls, and prostaglandins in gastriprotection by momordin Ic, an oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesions in rats. Life Sci 65:27–32CrossRefGoogle Scholar
  145. Matsuda H, Pongpiriyadacha Y, Morikawa T, Ochi M, Yoshikawa M (2003) Gastroprotective effects of phenylpropanoids from the rhizomes of Alpinia galanga in rats: structural requirements and mode of action. Eur J Pharmacol 471:59–67PubMedCrossRefGoogle Scholar
  146. Matsunaga T, Hasegawa C, Kawasuji T, Suzuki H, Saito H, Sagioka T, Takahashi R, Tsukamoto H, Morikawa T, Akiyama T (2000) Isolation of the antiulcer compound in essential oil from the leaves of Cryptomeria japonica. Biol Pharm Bull 23:595–598PubMedCrossRefGoogle Scholar
  147. Matsuo Y, Seki A, Yakabi K, Saziki R, Arai I, Isobe Y, Aihara H (1983) Effect of 2′-carboxymethoxy-4, 4′-bis(3-methyl-2-butenyloxy)chalcone (SU-88) on gastric local blood flow. Arzneimittelforschung 33:242–243PubMedGoogle Scholar
  148. McInerney BV (1991) Biologically active metabolites from Xenorhabdus spp., part 2. Benzopyran-1-one derivatives with gastroprotective activity. J Nat Prod 54:785–795PubMedCrossRefGoogle Scholar
  149. Mei X, Luo X, Xu S, Xu D, Zheng Y, Xu S, Lv J (2009) Gastroprotective effects of a new zinc(II)-curcumin complex against pylorus-ligature-induced gastric ulcer in rats. Chem Biol Interact 181:316–321PubMedCrossRefGoogle Scholar
  150. Mei X, Xu D, Xu S, Zheng Y, Xu S (2011) Gastroprotective and antidepressant effects of a new zinc(II)-curcumin complex in rodent models of gastric ulcer and depression induced by stresses. Pharm Biochem Behav 99:66–74CrossRefGoogle Scholar
  151. Merchant JL (2007) Tales from the crypts: regulatory peptides and cytokines in gastrointestinal homeostasis and disease. J Clin Invest 117:6–12PubMedCrossRefGoogle Scholar
  152. Minuz P, Cavallini G, Angelini GP, Lechi A, Brocco G, Riela A, Scuro LA, Velo GP (1984) Carbenoxolone and prostaglandin E2 and F gastric juice levels in man. Pharmacol Res Commun 16:875–884PubMedCrossRefGoogle Scholar
  153. Mitsui S, Kobayahi S, Nagahori H, Ogiso A (1976) Constituents from seeds of Alpinia galangal Wild. And their anti-ulcer activities. Chem Pharm Bull 24:2377–2382PubMedCrossRefGoogle Scholar
  154. Mochizuki S, Wakabayashi S, Tomiyama A, Satake N, Shibata S (1989) Thromboxane A2 antagonistic action of a new anti-ulcer agent, azuletil sodium (KT1-32). Scand J Gastroenterol Suppl 162:194–197PubMedCrossRefGoogle Scholar
  155. Mojžiš J, Hviščová K, Germanová D, Bukovičová D, Mirossay L (2001) Protective effect of quercetin on ischemia/reperfusion-induced gastric mucosal injury in rats. Physiol Res 50:501–506PubMedGoogle Scholar
  156. Moon HI, Lee YC, Lee JH (2011) Phenol glycosides with in vitro anti-Helicobacter pylori activity from Hypericum erectum Thunb. Phytohter Res 25:1389–1391Google Scholar
  157. Moraes TM, Kushima H, Moleiro FC, Santos RC, Rocha LRM, Marques MO, Vilegas W, Hiruma-Lima CA (2009) Effects of limonene and essential oil from Citrus aurantium on gastric mucosa: role of prostaglandins and gastric mucus secretion. Chem Biol Interact 180:499–505PubMedCrossRefGoogle Scholar
  158. Mori J, Hayashi T, Iwashima M, Matsunaga T, Saito H (2006) Effects of plastoquinones from the brown alga Sargassum micracanthum and a new chromene derivative converted from the plastoquinones on acute gastric lesions in rats. Biol Pharm Bull 29:1197–1201PubMedCrossRefGoogle Scholar
  159. Morikawa T, Matsuda H, Yamaguchi I, Pongpiriyadacha Y, Yoshikawa M (2004) New amides and gastroprotective constituents from the fruit of Piper chaba. Planta Med 70:152–159PubMedCrossRefGoogle Scholar
  160. Mota KSL, Dias GEN, Pinto MEF, Luiz-Ferreira A, Souza-Brito ARM, Hiruma-Lima CA, Barbosa-Filho JM, Batista LM (2009) Flavonoids with gastroprotective activity. Molecules 14:979–1012PubMedCrossRefGoogle Scholar
  161. Motilva V, Alarcón de la Lastra C, Martín MJ (1994) Ulcer-protecting effects of naringenin on gastric lesions induced by ethanol in rat: role of endogenous prostglandins. J Pharm Pharmacol 46:91–94PubMedCrossRefGoogle Scholar
  162. Murakami K, Okajima K, Harada N, Isobe H, Liu W, Johno M, Okabe H (1999a) Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation. Aliment Pharmacol Ther 13:521–530PubMedCrossRefGoogle Scholar
  163. Murakami S, Kijima H, Isobe Y, Muramatsu M, Aihara H, Otomo S, Lian-niang L, Chun-bo A (1990) Effect of salvianolic acid A, a depside from roots of Salvia miltiorrhiza, on gastric H + , K + -ATPase. Planta Med 56:360–363PubMedCrossRefGoogle Scholar
  164. Murakami S, Muramatsu M, Aihara H, Honda A, Mori Y (1987) Enzymatic sulfation of gastric mucous glycoprotein in rat–changes in glycoprotein sulfotransferase activity with stress and anti-ulcer agent, sofalcone. Res Commun Chem Pathol Pharmacol 57:77–98PubMedGoogle Scholar
  165. Murakami S, Muramatsu M, Hironaka A, Otomo S (1991) Inhibition of gastric H+ , K+-ATPase by the anti-ulcer agent, sofalcone. Biochem Pharmacol 42:1447–1451PubMedCrossRefGoogle Scholar
  166. Murakami S, Muramatsu M, Otomo S (1992) Gastric H+, K+-ATPase inhibition by catechins. J Pharm Pharmacol 44:926–928PubMedCrossRefGoogle Scholar
  167. Murakami T, Nakamura J, Matsuda H, Yoshikawa M (1999b) Bioactive saponins and glycoside. XV. Saponin constituents with gastriprotective effect from the seeds of tea plant, Camellia sinensis L. var. assamica Pierre, cultivated in Sri Lanka: structures of assamsaponins A, B, C, D, and E. Chem Pharm Bull 47:1759–1764PubMedCrossRefGoogle Scholar
  168. Muramatsu M, Tanaka M, Murakami S, Aihara H (1987) Inhibition of 15-hydroxy prostaglandin dehydrogenase and increase of prostaglandin E2: effects of sofalcone on rat gastric mucosa. Life Sci 41:315–322PubMedCrossRefGoogle Scholar
  169. Murata H, Kawano S, Tsuji S, Kamada T, Matsezawa Y, Katsu K, Inoue K, Kobayashi K, Mitsufuji S, Bamba T, Kawasaki H, Kajiyama G, Umegaki E, Inoue M, Saito I (2003) Combination therapy of ecabet sodium and cimetidine compared with cimetidine alone for gastric ulcer: prospective randomized multicenter study. J Gastroenterol Hepatol 18:1029–1033PubMedCrossRefGoogle Scholar
  170. Nagaoka M, Shibata H, Kimura-Takagi I, Hashimoto S, Aiyama R, Ueyama S, Yokokura T (2000) Anti-ulcer effects and biological activities of polysaccharides from marine algae. BioFactors 12:267–274PubMedCrossRefGoogle Scholar
  171. Naik Y, Jayaram S, Nayaka MAH, Lakshman DharmeshSM (2007) Gastroprotective effect of swallow root (Decalepis hamiltonii) extract: possible involvement of H(+)-K(+)-ATPase inhibition and antioxidative mechanism. J Ethnopharmacol 112:173–179PubMedCrossRefGoogle Scholar
  172. Najm WI (2011) Peptic ulcer disease. Prim Care Clin Office Pract 38:383–394CrossRefGoogle Scholar
  173. Nakamura M, Akiba Y, Oda M, Ishii H (1997) Alteration of basic fibroblast gorwth factor concentration and immunoreactivity in healing of ethanol-induced gastric mucosal damage: effect of sofalcone. J Clin Gastroenterol 25:S13–S20PubMedCrossRefGoogle Scholar
  174. Nanjundaiah SM, Annaiah HN, Dharmesh S (2009) Gastroprotective Effect of ginger rhizome (Zingiber officinale) extract: role of gallic acid and cinnamic acid in H(+), K(+)-ATPase/H. pylori inhibition and anti-oxidative mechanism. Evid Based Complem Alternat Med 2011:249487Google Scholar
  175. Navarrete A, Trejo-Miranda JL, Reyes-Trejo L (2002) Principles of root bark of Hippocratea excelsa (Hippocrataceae) with gastroprotective activity. J Ethnopharmacol 79:383–388PubMedCrossRefGoogle Scholar
  176. Niiho Y, Yamazaki T, Nakajima Y, Yamamoto T, Ando H, Hirai Y, Toriizuka K, Ida Y (2006) Gastroprotective effects of bitter principles isolated from gentian root and swertia herb on experimentally-induced gastric lesions in rats. J Nat Med 60:82–88CrossRefGoogle Scholar
  177. Njar VCO, Adesanwo JK, Raji Y (1995) Methyl angolensate: the antiulcer agent of the stem bark of Entandrophragma angolense. Planta Med 61:91–92PubMedCrossRefGoogle Scholar
  178. Nosálová V, Machová J, Babulová A (1993) Protective action of vinpocetine against experimentally induced gastric damage in rats. Arzneimittelforschung 43:981–985PubMedGoogle Scholar
  179. Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, Kazaz C (2006) Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol 103:59–65PubMedCrossRefGoogle Scholar
  180. Ohta Y, Kamiya Y, Imai Y, Arisawa T, Nakano H (2005) Plaunotol prevents the progression of acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats. Pharmacology 74:182–192PubMedCrossRefGoogle Scholar
  181. Okunrobo LO, Usifoh CO, Uwaya JO (2006) Anti-inflammatory and gastroprotective properties of some chalcones. Acta Pol Pharm 63:195–199PubMedGoogle Scholar
  182. Onoda Y, Magaribuchi T, Tamaki H (1989) Effects of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastric secretion and experimental ulcers in rats. Jpn J Pharmacol 51:65–73PubMedCrossRefGoogle Scholar
  183. Onoda Y, Takido M, Magaribuchi T, Tamaki H (1990) Effect of 12-sulfodehydroabietic acid monosodium salt (TA-2711), a new anti-ulcer agent, on gastri mucosal lesions induced by necrotizing agents and gastric mucosal defensive factors in rats. Jpn J Pharmacol 52:631–638PubMedCrossRefGoogle Scholar
  184. Ononiwu IM, Ibeneme CE, Ebong OO (2002) Effects of piperine on gastric acid secretion in albino rats. Afr J Med Med Sci 31:293–295PubMedGoogle Scholar
  185. Parmar NS, Tariq M, Ageel AM (1987) Studies on the possible mechanism of morphine-induced potentiation of the gastroulcerogenic effect of indomethacin in rats. Arch Int Pharmacodyn Ther 289:149–160PubMedGoogle Scholar
  186. Paulose-Ram R, Hirsch R, Dillon C, Gu Q (2005) Frequent monthly use of selected non-prescription and prescription non-narcotic analgesics among U.S. adults. Pharmacoepidemiol Drug Saf 14:257–266PubMedCrossRefGoogle Scholar
  187. Pearson JP, Roberts NB (2001) Mucosal protective effects of ecabet sodium: pepsin inhibition and interaction with mucus. Clin Sci 100:411–417PubMedCrossRefGoogle Scholar
  188. Peng J, Li Y (2010) The vanilloid receptor TRPV1: role in cardiovascular and gastrointestinal protection. Eur J Pharmacol 627:1–7PubMedCrossRefGoogle Scholar
  189. Pertino M, Rodríguez JA, Theoduloz C, Razmilic I, Schmeda-Hirschmann G (2006) Gastroprotective activity and cytotoxic effect of cyperenoic acid derivatives. J Pharm Pharmcol 58:1507–1513CrossRefGoogle Scholar
  190. Pertino M, Schmeda-Hirschmann G, Rodríguez JA (2007) Theoduloz C (2007) Gastroprotective effect and cytotoxicity of terpenes from the Paraguayan crude drug “yagua nova” (Jatropha isabelli). J Ethnopharmacol 111:553–559PubMedCrossRefGoogle Scholar
  191. Pertino MW, Theoduloz C, Rodríguez JA, Yáñez T, Lazo V, Schmeda-Hirschmann G (2010) Gastroprotective effect of carnosic acid γ-lactone derivatives. J Nat Prod 73:639–643PubMedCrossRefGoogle Scholar
  192. Pinder RM, Brogden RN, Sawyer PR, Speight TM, Spencer R, Avery GS (1976) Carbonoxole: a review of its pharmacologica properties and therapeutic efficacy in peptic ulcer disease. Drugs 11:245–307PubMedCrossRefGoogle Scholar
  193. Piotrowski J, Yamaki K, Tamura S, Slomiany A, Slomiany BL (1991) Enhancement of the physicochemical qualities of gastric mucus by sofalcone. J Physiol Pharmacol 42:193–304Google Scholar
  194. Pongipiriyadacha Y, Matsuda H, Morikawa T, Asao Y, Yoshikawa M (2003) Protective effects of polygodial on gastric mucosal lesions induced by necrotizing agents in rats and the possible mechanisms of action. Biol Pharm Bull 26:651–657CrossRefGoogle Scholar
  195. Ramakrishman K, Salinas RC (2007) Peptic ulcer disease. Am Fam Phys 76:1005–1012Google Scholar
  196. Rao CV, Vijayakumar M (2007) Protective effect of (+)-catechin against gastric mucosal injury induced by ischaemia-reperfusion in rats. J Pharm Pharmacol 59:1103–1107PubMedCrossRefGoogle Scholar
  197. Rask-Madsen J, Bukhave K, Madsen PER, Bekker C (1983) Effect of carbenoxolone on gastric prostaglandin E2 levels in patients with peptic ulcer disease following vagaland pentagastrin stimulation. Eur J Clin Invest 13:351–356PubMedCrossRefGoogle Scholar
  198. Rees WD, Garner A, Heylings JR, Flemström G (1981) Effect of carbenoxolone on alkaline secretion by isolated amphibian gastri and duodenal mucosa. Eur J Clin Invest 11:481–486PubMedCrossRefGoogle Scholar
  199. Reimann HJ, Lorenz W, Fischer M, Frölich R, Meyer HJ (1977) Histamine and acute haemorrhagic lesions in rat gastric mucosa: prevention of stress ulcer formation by (+)-catechin, an inhibitor of specific histidine decarboxylase in vitro. Agents Actions 7:69–73PubMedCrossRefGoogle Scholar
  200. Reyes-Chilpa R, Baggio CH, Alavez-Solano D, Kauffman FC, Sanchez RI, Mesia-Vela S (2006) Inhibition of gastric H + , K + -ATPase activity by flavonoids, coumarins and xanthones isolated from Mexican medicinal plants. J Ethnopharmacol 105:167–172PubMedCrossRefGoogle Scholar
  201. Reyes-Trejo B, Sánchez-Mendoza ME, Becerra-Garcia AA, Cedillo-Portugal E, Castillo-Henkel C, Arrieta J (2008) Bioassay-guided isolation of na anti-ulcer diterpenoid from Croton reflexifolius:role of nitric oxide, prostaglandins and sulfhydryls. J Pharm Pharmacol 60:931–936PubMedCrossRefGoogle Scholar
  202. Rios ERV, Rocha NFM, Venâncio ET, Moura BA, Feitosa ML, Cerqueira GS, Soares PMG, Woods DJ, Sousa FCF, Leal LKAM, Fonteles MMF (2010) Mechanisms involved in the gastroprotective activity of esculin on acute gastric lesions in mice. Chem Biol Interact 188:246–254PubMedCrossRefGoogle Scholar
  203. Roberts NB, Taylor WH (1980) The actions of carbenoxolone on enzymes and their relation to its therapeutic effect. Scand J Gastroenterol Suppl 65:11–17PubMedGoogle Scholar
  204. Rocha NFM, Venâncio ET, Moura BA, Silva MIG, Aquino-Neto MR, Rios ERV, Sousa DP, Vasconcelos SMM, Fonteles MMF, Sousa FCF (2010) Gastroprotection of (−)-α-bisabolol on acute gastric mucosal lesions in mice: the possible involved pharmacological mechanisms. Fundam Clin Pharmacol 24:63–71CrossRefGoogle Scholar
  205. Rodrigues PA, Morais SM, Souza CM, Silva ARA, Andrade GM, Silva MGV, Albuquerque RL, Rao VS, Santos FA (2010) Gastroprotective effect of barbatusin and 3-beta-hydroxy-3-deoxibarbatusin, quinonoid diterpenes isolated from Plectranthus grandis, in ethanol-induced gastric lesions in mice. J Ethnopharmacol 127:725–730CrossRefGoogle Scholar
  206. Rodríguez JA, Bustamante C, Astudillo L, Schmeda-Hirschmann G (2002) Gastroprotective activity of solidagenone on experimentally-induced gastric lesions in rats. J Pharm Pharmacol 54:399–404PubMedCrossRefGoogle Scholar
  207. Rodríguez JA, Hiruma-Lima CA, Brito ARMS (2004) Antiulcer activity and subacute toxicity of trans-dehydrocrotonin from Croton cajucara. Hum Exp Toxicol 23:455–461PubMedCrossRefGoogle Scholar
  208. Rodríguez JA, Theoduloz C, Sánchez M, Yáñez T, Razmilic I, Schmeda-Hirschmann G (2005) Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice. J Pharm Pharmacol 57:265–271PubMedCrossRefGoogle Scholar
  209. Rozza AL, Moraes TM, Kushima H, Tanimoto A, Marques MOM, Bauab TM, Hiruma-Lima CA, Pellizzon CH (2011) Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and β-pinene: involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E2. Chem Biol Interact 189:82–89PubMedCrossRefGoogle Scholar
  210. Rüegg T, Calderón AI, Queiroz EF, Solís PN, Marston A, Rivas F, Ortega-Barría E, Hostettmann K, Gupta MP (2006) 3-Farnesyl-2-hydroxybenzoic acid is a new anti-Helicobacter pylori compound from Piper multiplinervium. J Ethnopharmacol 103:461–467PubMedCrossRefGoogle Scholar
  211. Sachs G, Shin JM, Hunt R (2010) Novel approaches to inhibition of gastric acid secretion. Curr Gastroenterol Rep 12:437–447PubMedCrossRefGoogle Scholar
  212. Sachs G, Shin JM, Vagin O, Lambrecht N, Yakubov I, Munson K (2007) The gastric H, K ATPase as a drug target: past, present, and future. J Clin Gastroenterol 41:S226–S242PubMedCrossRefGoogle Scholar
  213. Safak B, Ciftci IH, Ozdemir M, Kiyildi N, Centikaya Z, Aktepe OC, Altindis M, Asik G (2009) In vitro anti-Helicobacter pylori activity of usnic acid. Phytother Res 23:955–957PubMedCrossRefGoogle Scholar
  214. Sánchez-Mendoza ME, Reyes-Ramírez A, Antonio LC, Jiménez LM, Rodríguez-Silverio J, Arrieta J (2011) Bioassay-guided isolation of na anti-ulcer compound, tagitinin C, from Tithonia diversifolia: role of nitric oxide, prostaglandinds and sulfhydryls. Molecules 16:665–674PubMedCrossRefGoogle Scholar
  215. Sánchez-Mendoza ME, Reyes-Trejo B, Sánchez-Gómez P, Rodríguez-Silverio J, Castillo-Henkel C, Cervantes-Cuevas H, Arrieta J (2010) Bioassay-guided isolation of na anti-ulcer chromene from Eupatorium aschenbornianum: role of nitric oxide, prostaglandins and slfhydryls. Fitoterapia 81:66–71PubMedCrossRefGoogle Scholar
  216. Santin JR, Lemos M, Klein-Júnior LC, Machado ID, Costa P, de Oliveira AP, Tilia C, de Souza JP, de Sousa JPB, Bastos JK, Andrade SF (2011) Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn Schmiedebergs Arch Pharmacol 383:149–158PubMedCrossRefGoogle Scholar
  217. Santin JR, Lemos M, Klein-Júnior LC, Niero R, Andrade SF (2010) Antiulcer effects of Achyrocline satureoides (Lam.) DC (Asteraceae) (Marcela), a folk medicine plant, in different experimental models. J Ethnopharmacol 130:334–339PubMedCrossRefGoogle Scholar
  218. Santos FA, Rao VSN (2001) 1, 8-Cineol, a food flavoring agent, prevents ethanol-induced gastric injury in rats. Dig Dis Sci 46:331–337PubMedCrossRefGoogle Scholar
  219. Sarosiek J, Bilski J, Tsukada H, Slomiany A, Slomiany BL (1987) Effect of solon on gastric mucus viscosity, permeability to hydrogen ion, and susceptibility to pepsion. Digestion 37:238–246PubMedCrossRefGoogle Scholar
  220. Sartori NT, Canepelle D, Sousa-Júnior PT, Martins DTO (1999) Gastroprotective effect from Calophyllum brasiliense Camb. bark on experimental gastric lesions in rats and mice. J Ethnopharmacol 67:149–156PubMedCrossRefGoogle Scholar
  221. Satyanarayana MN (2006) Capsaicin and gastric ulcers. Crit Rev Food Sci Nutr 46:275–328PubMedCrossRefGoogle Scholar
  222. Sawraj S, Bhardawaj TR, Sharma PD (2010) Design, synthesis and evaluation of novel indomethacin-flavonoid mutual prodrugs as safer NSAIDs. Med Chem Res 20:687–694CrossRefGoogle Scholar
  223. Saziki R, Arai I, Isobe Y, Hirose H, Aihara H (1984) Effects of sofalcone on necrotizing agents-induced gastric lesions and on endogenous prostaglandins in rats stomachs. J Pharmacobiodyn 7:791–797PubMedCrossRefGoogle Scholar
  224. Schmeda-Hirschmann G, Yesilada E (2005) Traditional medicine and gastroprotective crude drugs. J Ethnopharmacol 100:61–66Google Scholar
  225. Schmeda-Hirschmann G, Yesilada E (2010) Traditional medicine and gastroprotective crude drugs. J Ethnopharmacol 100:61–66CrossRefGoogle Scholar
  226. Schubert ML, Peura DA (2008) Control of gastric acid secretion in health and disease. Gastroenterology 134:1842–1860PubMedCrossRefGoogle Scholar
  227. Schultz C, Bossolani MP, Torres LMB, Lima-Landman MTR, Lapa AJ, Souccar C (2007) Inhibition of the gastric H+ , K+-ATPase by plectrinone A, a diterpenoid isolated from Plectranthus barbatus Andrews. J Ethnopharmacol 111:1–7PubMedCrossRefGoogle Scholar
  228. Schwamberger K, Reissigi H (1980) Carbenoxolone patients with gastric ulcers. A double-blind trial. Scand J Gastroenterol Suppl 65:59–62PubMedGoogle Scholar
  229. Scoto GM, Parenti C, Scoto E, Spadaro C, Arrigo-Reina R (1991) Effect of indomethacin on opioid-induced gastric protection in cold-restrained stress. Life Sci 48:867–871PubMedCrossRefGoogle Scholar
  230. Shakeerabanu M, Sujatha K, Praveen Rajneesh C, Manimaran A (2011) The defensive effect of quercetin on indomethacin induced gastric damage in rats. Adv Biol Res 5:64–70Google Scholar
  231. Sheen E, Triadafilopoulos G (2011) Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 56:931–950PubMedCrossRefGoogle Scholar
  232. Shibata H, Kimura-Takagi I, Nagaoka M, Hashimoto S, Aiyama R, Iha M, Ueyama S, Yokokura T (2000) Properties of fucoidan from Cladosiphon okamuranus tokida in gastric mucosal protection. BioFactors 11:235–245PubMedCrossRefGoogle Scholar
  233. Shibata H, Nagaoka M, Takagi I, Hashimoto S, Aiyama R, Yokokura T (2001) Effect of oligofucose derivatives on acetic acid-induced gastric ulcer in rats. Bio Med Mater Eng 11:55–61Google Scholar
  234. Shiratori K, Watanabe S, Takeuchi T (1993) Role of endogenous prostaglandins in secretin- and plaunotol-induced inhibition of gastric acid secretion in the rat. Am J Gastroenterol 88:84–89PubMedGoogle Scholar
  235. Shiratori K, Watanabe S-I, Takeuchi T, Shimizu K (1990) Plaunotol inhibitis postprandial gastrin release by its unique secretin-releasing action in humans. Dig Dis Sci 35:1140–1145PubMedCrossRefGoogle Scholar
  236. Silva BP, Parente JP (2010) Chemical properties and antiulcerogenic activity of a galactomannoflucan from Syagrus oleracea. Food Chem 123:1076–1080CrossRefGoogle Scholar
  237. Silva MIG, Moura BA, Aquino-Neto MR, Tomé AR, Rocha NFM, Carvalho AMR, Macedô DS, Vasconcelos SMM, Sousa DP, Viana GSB, Sousa FCF (2009) Gastroprotective activity of isopulegol on experimentally induced gastric lesions in mice: investigation of possible mechanisms of action. Naunyn-Schmiedeberg’s Arch Pharmacol 380:233–245CrossRefGoogle Scholar
  238. Singh N, Shukla N, Singh P, Sharma R, Rajendran SM, Maurya R, Palit G (2010) Verbascoside isolated from Tectona grandis mediates gastric protection in rats via inhibiting proton pump activity. Fitoterapia 81:755–761PubMedCrossRefGoogle Scholar
  239. Singh S, Majumdar DK (1999) Evaluation of the gastric antiulcer activity of fixed oil of Ocimum sanctum (Holy Basil). J Ethnopharmacol 65:13–19PubMedCrossRefGoogle Scholar
  240. Sisodia SS, Tanwar YS, Bhatnagar M (2005) Gastric antiulcer activity of rutin and quercetin. Indian Pharm 4:89–91Google Scholar
  241. Slomiany BL, Liau YH, Mizuta K, Slomiany A (1987a) Fatty acid acylation of mucin by gastric mucosa. Effects of sofalcone and sucralfate. Biochem Pharmacol 36:3273–3276PubMedCrossRefGoogle Scholar
  242. Slomiany BL, Liau YH, Carter SR, Sarosiek J, Tsukada H, Slomiany A (1987b) Enzymatic sulfation of mucin in gastric mucosa: effect of sofalcone, sucralfate and aspirin. Digestion 38:178–186PubMedCrossRefGoogle Scholar
  243. Srikanta BM, Nayaka MAH, Dharmesh SM (2011) Inhibition of Helicobacter pylori growth and its cytotoxicity by 2-hydroxy-4-methoxy-benzaldehyde of Decalepis hamiltonii (Wight & Arn); a new functional attribute. Biochimie 93:678–688PubMedCrossRefGoogle Scholar
  244. Strauss RJ, Stein TA, Mandell C, Wide L (1978) Cimetidine, carbenoxolone sodium, and antacids for the prevention of experimental stress ulcers. Arch Surg 113:858–862PubMedCrossRefGoogle Scholar
  245. Sun X, Matsumoto T, Yamada H (1992) Purification of an anti-ulcer polysaccharide from the leaves of Panax ginseng. Planta Med 58:445–448PubMedCrossRefGoogle Scholar
  246. Suzuki Y, Ishihara M, Segami T, Ito M (1998) Anti-ulcer effects of antioxidants, quercetin, α-tocopherol, nifedipine and tetracycline in rats. Jpn J Pharmacol 78:435–441PubMedCrossRefGoogle Scholar
  247. Swarbakar S, Ganguly K, Kundu P, Banerjee A, Maity P, Sharma AV (2005) Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem 280:9409–9415CrossRefGoogle Scholar
  248. Tada H, Yasuda F, Otani K, Doteuchi M, Ishihara Y, Shiro M (1991) New antiulcer quassinoids from Eurycoma longifolia. Eur J Med Chem 26:345–349CrossRefGoogle Scholar
  249. Takahashi M, Hata Y, Terano A (1997) Effect of sofalcone on the expression of hepatocyte growth factor (HGF) and a brief review of HGF in the stomach. J Clin Gastroenterol 25:S21–S27PubMedCrossRefGoogle Scholar
  250. Takahashi M, Maeda S, Ogura K, Terano A, Omata M (1998) The possible role of vascular endothelial growth factor (VEGF) in gastric ulcer healing: effect of sofalcone on VEGF in vitro. J Clin Gastroenterol 27:S178–S182PubMedCrossRefGoogle Scholar
  251. Takekawa S, Matsui T, Arakawa YJ (2006) The protective effect of the soybean polyphenol genistein against stress-induced gastric mucosal lesions in rats, and its hormonal mechanisms. Nutr Sci Vitaminol 52:274–280CrossRefGoogle Scholar
  252. Takeuchi K, Tanaka T, Wakabayashi S, Mochizuki S, Tomiyama A, Okabe S (1990) Effects of topical application of KT1–32 on transmucosal potential difference and acid secretion in the rat stomach. Jpn J Pharmacol 54:227–235PubMedCrossRefGoogle Scholar
  253. Takeuchi K (2010) Prostaglandin EP receptors and their roles in mucosal protection and ulcer healing in the gastrointestinal tract. Adv Clin Chem 51:121–144PubMedCrossRefGoogle Scholar
  254. Tanaka LYA, Oliveira AJB, Gonçalves JE, Cipriani TR, Souza LM, Marques MCA, Werner MFP, Baggio CH, Gorin PAJ, Sassaki GL, Iacomini M (2010) An arabinogalactan with anti-ulcer protective effects isolated from Cereus peruvianus. Carbohydr Polym 82:714–721CrossRefGoogle Scholar
  255. Tanaka N, Kashiwada Y, Nakano T, Shibata H, Higuchi T, Sekiya M, Ikeshiro Y, Takaishi Y (2009) Chromone and chromanone glucoside from Hypericum sikokumontanum and their anti-Helicobacter pylori activities. Phytochemistry 70:141–146PubMedCrossRefGoogle Scholar
  256. Tatsugami M, Ito M, Ishihara K, Haruma K, Sumii M, Sasaki A, Kitamura S, Takamura A, Wada Y, Matsumoto Y, Imagawa S, Takata S, Tanaka S, Yoshihara M, Chayama K (2011) Plaunotol induced a comparative increase of acidic mucin fraction in gastric juice. Hepatogastroenterology 58:663–668PubMedGoogle Scholar
  257. Tazi-Saad K, Chariot J, Vatier J, Del Tacca M, Rozé C (1991) Antisecretory and anti-ulcer effects of morphine in rats adter gastric mucosal aggression. Eur J Pharmacol 192:271–277PubMedCrossRefGoogle Scholar
  258. Torrado S, Torrado S, Agis A, Jimenez ME, Cadórniga R (1995) Effect of dissolution profile and (−)-α-bisabolol on the gastrotoxicity of acetylsalicyclic acid. Pharmazie 50:141–143Google Scholar
  259. Tournier H, Schinella G, Balsa EM, Buschiazzo H, Mañez S, Buschiazzo PM (1999) Effect of the chloroform extract of Tanacetum vulgare and one of its active principles, parthenolide, on experimental gastric ulcer in rats. J Pharm Pharmacol 51:215–219PubMedCrossRefGoogle Scholar
  260. Tuo B, Wen G, Song P, Xu J, Liu X, Seidler U, Dong H (2011) Genistein stimulates duodenal HCO3 secretion through PI3K pathway in mice. Eur J Pharmacol 651:159–167PubMedCrossRefGoogle Scholar
  261. Tuorkey M, Karolin K (2009) Anti-ulcer activity of curcumin on experimental gastric ulcer in rats and its effect on oxidative stress/antioxidant, IL-6 and enzyme activities. Biomed Environ Sci 22:488–495PubMedCrossRefGoogle Scholar
  262. Ushiyama S, Matsuda K, Asai F, Yamazaki M (1987) Stimulation of prostaglandin production by (2E, 6Z, 10E)-7-hydroxymethyl-3, 11, 15-trimethyl-2, 6, 10, 14-hexadecatatraen-1-ol (plaunotol), a new anti-ulcer drug, in vitro and in vivo. Biochem Pharmacol 36:369–375PubMedCrossRefGoogle Scholar
  263. Ustün O, Ozçelik B, Akyön Y, Abbasoglu U, Yesilada E (2006) Flavonoids with anti-Helicobacter pylori activity from Cistus laurifolius leaves. J Ethnopharmacol 108:457–461PubMedCrossRefGoogle Scholar
  264. Vapaatalo H, Lindén I, Metsä-Ketelä T, Kangasaho M, Laustiola K (1978) Effect of carbenoxolone on phosphodiesterase and prostaglandin synthetase activities. Experientia 34:384–385PubMedCrossRefGoogle Scholar
  265. Vega AE, Wendel GH, Maria AOM, Pelzer L (2009) Antimicrobial activity of Artemisia douglasiana and dehydroleucodine against Helicobacter pylori. J Ethnopharmacol 124:653–655PubMedCrossRefGoogle Scholar
  266. Wada K, Kamisaki Y, Nakamoto K, Kishimoto Y, Ashida K, Itoh T (1997) Effect of plaunotol on gastric injury induced by ischaemia-reperfusion in rats. J Pharm Pharmacol 49:903–907PubMedCrossRefGoogle Scholar
  267. Waisman Y, Marcus H, Ligumski M, Dinari G (1991) Modulation by opiates of small intestinal prostaglandin E2 and 3′, 5′ cyclic adenosine monophosphate levels and of indomethacin-induced ulceration in the rat. Life Sci 48:2035–2042PubMedCrossRefGoogle Scholar
  268. Wallace JL, Miller MJS (2000) Nitric oxide in mucosal defense: a little goes a long way. Gastroenterology 119:512–520PubMedCrossRefGoogle Scholar
  269. Wang J, Zhu L, Zou K, Cheng F, Dan F, Guo Z, Cai Z, Yang J (2009) The anti-ulcer activities of bisabolangelone from Angelica polymorpha. J Ethnopharmacol 123:343–346PubMedCrossRefGoogle Scholar
  270. Wang KT, Chen LG, Wu CH, Chang CC, Wang CC (2010) Gastroprotective activity of atractylenolide III from Atractylodes ovata on ethanol-induced gastric ulcer in vitro and in vivo. J Pharm Pharmacol 62:381–388PubMedCrossRefGoogle Scholar
  271. Wang L, Hu C, Deng P, Shen S, Zhu H, Ding J, Tan G, Li Y (2005) The protective effects of rutaecarpine on gastric mucosa injury in rats. Planta Med 71:416–419PubMedCrossRefGoogle Scholar
  272. Wang L, Song L, Jiang XJ (2011) Quantification of sofalcone in human plasma and urine by high performance liquid chromatography–mass spectrometry. Pharm Biomed Anal 55:1179–1185CrossRefGoogle Scholar
  273. Wang Y, Huang T (2005) High-performance liquid chromatography for quantification of plumbagin, na anti-Helicobacter pylori compound of Plumbago zeylanica L. J Chromatogr A 1094:99–104PubMedCrossRefGoogle Scholar
  274. Watanabe K, Yano S, Minakawa Y (1987) Morphine inhibits the gastric acid secretion stimulated by 2-deoxy-d-glucose via a central mechanism in anesthetized rats. Eur J Pharmacol 143:293–298PubMedCrossRefGoogle Scholar
  275. Wittschier N, Faller G, Hensel A (2009) Aqueous extracts and polysaccharides from Liquorice roots (Glycyrrhiza glabra L.) inhibit adhesuin of Helicobacter pylori to human gastric mucosa. J Ethnopharmacol 125:218–223PubMedCrossRefGoogle Scholar
  276. Yadav DK, Singh N, Dev K, Sharma R, Sahai M, Palit G, Maurya R (2011) Anti-ulcer constituents of Annona squamosa twigs. Fitoterapia 82:666–675PubMedCrossRefGoogle Scholar
  277. Yamada H, Sun X, Matsumoto T, Ra K, Hirano M, Kiyohara H (1991) Purification of anti-ulcer polysaccharides from the roots of Bupleurum falcatum. Planta Med 57:555–559PubMedCrossRefGoogle Scholar
  278. Yamahara J, Mochizuki M, Fujimura H, Takaishi Y, Yoshida M, Tomimatsu T, Tamai Y (1990) Antiulcer action of Sophora flavescens root and an active constituent. I. J Ethnopharmacol 29:173–177PubMedCrossRefGoogle Scholar
  279. Yano S, Horie S, Wakabayashi S, Mochizuki S, Tomiyama A, Watanabe K (1990) Increasing effect of sodium 3-ethyl-7-isopropyl-1-azulenesulfonate 1/3 hydrate (KT1–32), a novel antiulcer agent, on gastric mucosal blood flow in anesthetized. Res Commun Chem Pathol Pharmacol 70:253–256PubMedGoogle Scholar
  280. Yesilada E, Gürbüz I, Bedir E, Tatli I, Khan IA (2004) Isolation of anti-ulcerogenic sesquiterpene lactones from Centaurea solstitialis L. ssp. solstitialis through bioassay-guided fractionation procedures in rats. J Ethnopharmacol 95:213–219PubMedCrossRefGoogle Scholar
  281. Yeşilada E, Takaishi Y (1999) A saponin with anti-ulcerogenic effect from the flowers of Spartium junceum. Phytochemistry 51:903–908PubMedCrossRefGoogle Scholar
  282. Yin S, Fan C, Dong L, Yue J (2006) Psoracorylifols A-E, five novel compounds with activity against Helicobacter pylori from seeds of Psoralea corylifolia. Tetrahedron 62:2569–2575CrossRefGoogle Scholar
  283. Yoshikawa T, Nakamura S, Takahashi S, Naito Y, Kondo M (1993a) Effect of sofalcone on gastric mucosal injury induced by ischemia-reperfusion and its antioxidant properties. J Clin Gastroenterol 17:S111–S115PubMedCrossRefGoogle Scholar
  284. Yoshikawa M, Hatakeyama S, Inoue Y, Yamahara J (1993b) Saussureamines A, B, C, D, and E, new anti-ulcer principles from Chinese Saussureae radix. Chem Pharm Bull 41:214–216PubMedCrossRefGoogle Scholar
  285. Yoshikawa M, Hatakeyama S, Taniguchi K, Mauda H, Yamahara J (1992) 6-gingesulfonic acid, a new anti-ulcer principle, and gingerglycolipids A, B and C, three new monoacyldigalactosylglycerols, from Zingiberis rhizoma originating in Taiwan. Chem Pharm Bull 40:2239–2241PubMedCrossRefGoogle Scholar
  286. Zahorodnyĭ MI (2003) Effect of quercetin on sodium diclofenac-induced ulceration. Lik Sprava 1:96–99PubMedGoogle Scholar
  287. Zanatta F, Gandolfi RB, Lemos M, Ticona JC, Gimenez A, Clasen BK, Cechinel Filho V, Andrade SF (2009) Gastroprotective activity of alkaloid extract and 2-phenylquinoline obtained from the bark of Galipea longiflora Krause (Rutaceae). Chem Biol Interact 180:312–317PubMedCrossRefGoogle Scholar
  288. Zhang D, Du X, Liu M, Li H, Jiang Y, Zhao L, Gu J (2008) Determination of ecabet in human plasma by high-performance liquid chromatography-tandem mass spectrometry. J Chormatogr B 863:223–228CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Luiz Carlos Klein-Júnior
    • 1
  • José Roberto Santin
    • 1
  • Rivaldo Niero
    • 1
  • Sérgio Faloni de Andrade
    • 1
  • Valdir Cechinel-Filho
    • 1
  1. 1.Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-FarmacêuticasUniversidade do Vale do Itajaí, UNIVALIItajaíBrazil

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