QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY

Authors

  • SOHEIR E KOTOB Department of Hormones, National Research Centre, Dokki, Giza, Egypt
  • Alaa H Sayed Department of Hormones, National Research Centre, Dokki, Giza, Egypt
  • Safaa H Mohamed Department of Hormones, National Research Centre, Dokki, Giza, Egypt
  • Hanaa H Ahmed Department of Hormones, National Research Centre, Dokki, Giza, Egypt

DOI:

https://doi.org/10.22159/ajpcr.2018.v11i1.21991

Keywords:

Gastric ulcer, Omeprazole, Quercetin, Ellagic acid, Aspirin, Rats

Abstract

 

 Objective: The present study was initiated to describe the gastroprotective role of quercetin (Qu) and ellagic acid (EA) on aspirin-induced gastric ulcer (GU) in rats.

Methods: Forty adult female albino rats of Wistar strain were distributed into: Control group, GU group, Omeprazole group, Qu group, and EA group. Gross examination, biochemical analyses including serum adrenocorticotropic hormone (ACTH), serotonin (ST), ferritin, heme oxygenase-1 (HO-1), interleukin-2 (IL-2), advanced glycosylation end products (AGEs), and fibronectin (FN) levels were estimated. Moreover, histopathological and histochemical examinations of stomach tissue samples were carried out.

Results: Gross examination of gastric mucosa of rats in GU group revealed hyperemia of the stomach mucosa. Furthermore, rats in GU group experienced a significant rise in serum ACTH, ferritin, HO-1, IL-2 and AGEs levels accompanied with significant drop in serum ST and FN levels versus control counterparts. Pre-treatment of GU group with Omeprazole, Qu or EA caused marked improvement in the measured biochemical parameters. Histopathological and histochemical examinations of stomach tissue samples documented the protective action of Omeprazole, Qu and EA with different degrees against GU caused by aspirin.

Conclusion: As a conclusion to this study, we can state that both Qu and EA have gastroprotective effect against aspirin-induced GU in rat model. Of note, Qu showed superior impact than EA as an antiulcer agent in this study. The corresponding mechanisms are speculated to be associated with inhibiting stress-induced gastric lesion, attenuating the oxidative stress, iron chelation and blunting ferritin level, modulating inflammatory cascade, and promoting the healing process.

Downloads

Download data is not yet available.

References

Ghosh CK, Khan MR, Alam F, Shil BC, Kabir MS, Mahmuduzzaman M, et al. Peptic Ulcer disease in Bangladesh: A multi-centre study. Mymensingh Med J 2017;26:141-4.

Sharma D, Bhatt S. A comprehensive review on ulcer healing potential of medicinal plants. Int J Pharm Pharm Sci 2014;16 Suppl 10:1-9.

Casa CL, Villegas I, Lastra CA, Motilva V, Calero MJ. Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 2000;71:45-53.

Ray R, Chaudhuri R, Majumdar B, Bandyopadhyay S. Antioxidant activity of ethanol extract of rhizome of Picrorhiza kurroa on indomethacin induced gastric ulcer during healing. Indian J Clin Biochem 2002;17 Suppl 2:44-51.

Mallika J, Shyamala S. Antioxidant effect of methanolic extract of Solanum nigrum berries on aspirin induced gastric mucosal injury. Indian J Clin Biochem 2004;19 Suppl 1:57-61.

Cuzick J, Thorat MA, Bosetti C. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol 2015;26 Suppl 1:47-57.

Hern S, Ez-Dıa Z, Rodrıguez LA. Cardio protective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med 2006;4:22.

Dajani EZ, Klamut MJ. Novel therapeutic approaches to gastric and duodenal ulcers: An update. Expert Opin Investig Drugs 2000;9:1537-44.

Shin JM, Sachs G. Pharmacology of proton pump inhibitors. Curr Gastroenterol Rep 2008;10:528-34.

Robinson M, Horn J. Clinical pharmacology of proton pump inhibitors: What the practicing physician needs to know. Drugs 2003;63:2739-54.

Kedika RR, Souza RF, Spechler SJ. Potential anti-inflammatory effects of proton pump inhibitors: A review and discussion of the clinical implications. Dig Dis Sci 2009;54:2312-7.

Nathiya S, Durga M, Thiyagarajan D. Quercetin, encapsulated querxcetin and it application-a review. Int J Pharm Pharm Sci 2014;6:20-4.

Haleagrahara N, Radhakrishnan A, Lee N, Kumar P. Flavonoid quercetin protects against swimming stress-induced changes in oxidative biomarkers in the hypothalamus of rats. Eur J Pharmacol 2009;621:46-52.

Chan HM, Zhu LF, Zhong R, Grant D, Goyer RA, Cherian MG. Nephrotoxicity in rats following liver transplantation from cadmium-exposed rats. Toxicol Appl Pharmacol 1993;123:89-96.

Tauber AI, Fay JR, Marletta MA. Flavonoid inhibition of the human neutrophil NADPH-oxidase. Biochem Pharmacol 1984;33:1367-9.

Bureau G, Longpre F, Martinoli MG. Resveratrol and quercetin, two natural polyphenols, reduce apoptotic neuronal cell death induced by neuroinflammation. J Neurosci Res 2008;86:403-10.

Beil W, Birkholz C, Sewing KF. Effects of flavonoids on parietal cell acid-secretion, gastric mucosal prostaglandin production and Helicobacter pylori growth. Arzneim Forsch 1995;45:697-700.

Charest M, Belair MA. C13 urea breath test accuracy analysis against former C14 urea breath test technique: Is there still a need for an indeterminate result category. J Nucl Med Technol 2017;45 Suppl 2:87-90.

Vattem DA, Shetty K. Biological functionality of EA: A review. J Food Biochem 2005;29:234-66.

Khanduja KL, Gandhi RK, Pathania V, Syal N. Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice. Food Chem Toxicol 1999;37:313-8.

Rogerio AP, Fontanari C, Borducchi E, Keller AC, Russo M, Soares EG, et al. Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma. Eur J Pharmacol 2008;580:262-70.

Soh PN, Witkowski B, Olagnier D, Nicolau ML, Garcia-Alvarez M, Berry A, et al. In vitro and in vivo properties of ellagic acid in malaria treatment. Antimicrob Agents Chemother 2009;53:1100-6.

Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH. Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation. Exp Dermatol 2010;19:182-90.

Chao CY, Mong MC, Chan KC, Yin MC. Anti-glycative and anti-inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice. Mol Nutr Food Res 2010;54:388-95.

Han DH, Lee MJ, Kim JH Antioxidant and apoptosis inducing activities of EA. Anticancer Res 2006;26:3601-6.

Iino T, Nakahara K, Miki W, Kiso Y, Ogawa Y, Kato S, et al. Less damaging effect of whisky in rat stomachs in comparison with pure ethanol. Digestion 2001;64:214-221.

Chatterjee A, Chatterjee S, Bandyopadhyay SK. H. pylori-induced gastric ulcer: Pathophysiology and herbal remedy. Int J Biol Med Res 2012;3:1461-5.

Ogawa Y, Kanatsu K, Iino T, Kato S, Jeong YI, Shibata N, et al. Protection against dextran sulfate sodium-induced colitis by microspheres of ellagic acidin rats. Life Sci 2002;71:827-39.

Elsharabasy FS, AL-Mushhin AA, Araffa S, Farrag AH. Phytochemical screening and gastroprotective effect of the aerial parts of salasola terrandra forssk. Against aspirin induced gastric ulceration in rats. J Pharm Phytochem 2015;3 Suppl 6:221-32.

Carvalho CA, Fernandesk KM, Matta SL, Silva MB, Oliveira LL, Fonseca CC. Evaluation of antiulcerogenic activity of aqueous extract of Brassica oleracea var. Capitata (CABBAGE) on Wister rat gastric ulceration. Arq Gastroenterol 2011;48 Suppl 4:276-82.

Shakeerabanu M, Sujatha K, Rajneesh CP, Manimaran A. The defensive effect of quercetin on indomethacin induced gastric damage in rats. Adv Biol Res 2011;5 Suppl 1:64-70.

Chatterjee A, Chatterjee S, Das S, Saha A, Chattopadhyay S, Bandyopadhyay SK. Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation. Acta Biochim Biophys Sin 2012;44:565-76.

Van Herck H, Baumans V, Brandt CJ, Boere HA, Hesp AP, Lith HA, et al. Blood sampling from the retro-orbital plexus, the saphenous vein and the tail vein in rats: Comparative effects on selected behavioral and blood variables. Laboratory Anim 2001;35:131-9.

Ganguly AK. A method for quantitative assement of experimentally produced ulcers in stomach of rats. Experientia 1969;25:1124.

Suzuki Y, Hayashi M, Ito M, Yamagami I. Anti-ulcer effects of 4’-(2-carboxyetyl) phenyl trans-4-aminomethyl cyclohexane carboxylate hydrochloride (cetraxate) on various experimental gastric ulcers in rats. Jpn J Pharmacol 1976;26:471-80.

Odell WD, Horton R, Pandian MR, Wong J. The Use of ACTH and Cortisol Assays in the Diagnosis of Endocrine Disorders. ???: Nichols Institute Publication; 1989.

White D, Kramer D, Johnson G, Dick F, Hamilton H. CF: Enzyme immunoassay for the quantitative determination of human ferritin concentration in human serum. Am J Clin Path 1986;72:346.

Banchroft JD, Steven A, Turner DR. Theory and Practice of Histological Technique. 4th ed. New York, London, San Francisco, Tokyo: Churchil Livingstone; 1996.

Manus JF. Histological demonstration of mucin after periodic acid. Nature 1946;158:202.

Armitage P, Berry G. Comparison of several groups. In: Statistical Method in Medical Research. 2nd ed. Oxford: Block well Significant Publication; 1987. p. 186-213.

Rao V, Sairam K, Goel RK. Experimental evaluation of Bacopa monniera on rat gastric ulceration and secretion. Indian J Physiol Pharmacol 2000;44:35-41.

Lee M, Kallal SM, Feldman M. Omeprazole prevents indomethacin-induced gastric ulcers in rabbits. Aliment Pharmacol Ther 1996;10:571-6.

Alkushi AG, Elsawy NA. Quercetin attenuates indomethacin-induced acute gastric ulcer in rats. Folia Morphol (Warsz) 2017;76 Suppl 2:252-61.

Virchenko OV, Falalyeyeva TM, Beregova TV, Maryana SY. The multistrain probiotic enhances the healing process of stress-induced lesions of the gastric mucosa of ats. Res J Pharm Biol Chem Sci 2015;6 Suppl 1:249-59.

Ohta Y, Kaida S, Chiba S, Tada M, Teruya A, Imai Y, et al. Involvement of oxidative stress in increases in the serum levels of various enzymes and components in rats with water-immersion restraint stress. Clin Biochem Nutr 2009;45 Suppl 3:347-54.

Filaretova L, Morozova O, Bagaeva T, Podvigina TJ. From gastro protective to proulcerogenic action of glucocorticoids on the gastric mucosa. Physiol Pharmacol 2009;60 Suppl 7:79-86.

Berkenbosch F, Oers J, Rey A, Tilders F, Besedovsky H. Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science 1987;238:524-6.

Lam NP, Le PD, Crawford SY, Patel S. National survey of stress ulcer prophylaxis. Crit Care Med 1999;27:98-103.

Kawabata K, Kawai Y, Terao J. Suppressive effect of quercetin on acute stress-induced hypothalamic-pituitary-adrenal axis response in wistar rats. J Nutr Biochem 2009;21:374-80.

Naveen S, Siddalingaswamy M, Singsit D, Khanum F. Anti-depressive effect of polyphenols and omega-3 fatty acid from pomegranate peel and flax seed in mice exposed to chronic mild stress. Psychiatry Clin Neurosci 2013;67:501-8.

Al Asmari AA, Arshaduddin M, Elfaki I, Kadasah S, Al Robayan A, Al Asmary S. Aripiprazole an atypical antipsychotic protects against ethanol induced gastric ulcers in rats. Int J Clin Exp Med 2014;7 Suppl 8:2031-44.

Debnath S, Biswas D, Ray K, Guha D. Moringaoleifera induced potentiation of serotonin release by 5-HT3 receptors in experimental ulcer model. Phytomedicine 2011;18:91-5.

Cho CH, Lai KH, Ogle CW, Tsai YT, Lee SD, Lo KJ. The role of histamine and serotonin in gastric acid secretion: A comparative study in gastric and duodenal ulcer patients. J Gastroenterol Hepatol 1986;1 Suppl 6:437-42.

Lai YC, Ho Y, Huang KH, Tsai LH. Effects of erotonin on acid secretion in isolated rat stomach: The role of 5HT3 receptors. Chin J Physiol 2009;52:395-405.

Ji CX, Fan DS, Li W, Guo L, Liang ZL, Xu RM, et al. Evaluation of the anti-ulcerogenic activity of the antidepressants duloxetine, triptyline, fluoxetine and mirtazapine in different models of experimental gastric ulcer in rats. Eur J Pharmacol 2012;691:46-51.

Gjestad C, Westin AA, Skogvoll E, Spigset O. Effect of proton pump inhibitors on the serum concentrations of the selective serotonin reuptake inhibitors citalopram, escitalopram, and sertraline. Ther Drug Monit 2015;37:90-7.

Yoshino S, Hara A, Sakakibara H, Kawabata K, Tokumura A, Ishisaka A, et al. Effect of quercetin and glucuronide metabolites on the monoamine oxidase - A reaction in mouse brain mitochondria. Nutrition 2011;27:847-52.

Abdalla FH, Schmatz R, Andréia MC, Carvalho FB, Baldissarelli J, Oliveira JS, et al. Quercetin protects the impairment of memory and anxiogenic-like behavior in rats exposed to cadmium: Possible involvement of the acetyl cholinesterase and Na+, K+-ATPase activities. Physiol Behav 2014;135:152-67.

Girish C, Raj V, Arya J, Balakrishnan S. Evidence for the involvement of the monoaminergic system, but not the opioid system in the antidepressant-like activity of ellagic acid in mice. Eur J Pharmacol 2012;682:118-25.

Kalshetti P, Allurib R, Thakurdesaic P. Antidepressant and anti-anxiety effect of ellagic acid from Punica granatum L. rind in olfactory bulbectomy model in rats. Int J Pharm Sci Rev Res 2015;34 Suppl 1:197-204.

Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, et al. The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol 2005;518:40-6.

Eshraghian A. Epidemiology of Helicobacter pylori infection among the healthy population in Iran and countries of the Eastern Mediterranean region: A systematic review of prevalence and risk factors. World J Gastroenterol 2014;20 Suppl 46:17618-25.

Jamieson JA, Kuhnlein HV. The paradox of anemia with high meat intake: A review of the multifactorial etiology of anemia in the Inuit of North America. Nutr Etiol Rev 2008;66 Suppl 5:256-71.

Windle HJ, Kelleher D, Crabtree JE. Childhood Helicobacter pylori infection and growth impairment in developing countries: A vicious cycle? Pediatrics 2007;119:E754-9.

Miret S, Simpson RJ, McKie AT. Physiology and molecular biology of dietary iron absorption. Annu Rev Nutr 2003;23:283-301.

Sharma VR, Brannon MA, Carloss EA. Effect of omeprazole on oral iron replacement in patients with iron deficiency anemia. South Med J 2004;97:887-9.

Hutchinson C, Geissler CA, Powell JJ, Bomford A. Proton pump inhibitors suppress absorption of dietary non-heme iron in hereditary hemochromatosis. Gut 2007;56:1291-5.

Lesjak M, Hoque R, Balesaria S, Skinner V, Debnam ES. Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro. PLoS One 2014;9 Suppl 7:1-10.

Kim EY, Ham SK, Shigenaga MK, Han O. Bioactive dietary polyphenolic compounds reduce nonheme iron transport across human intestinal cell monolayers. J Nutr 2008;138:1647-51.

Guo JS, Cho CH, Wang WP, Shen XZ, Cheng CL, Koo MW. Expression and activities of three inducible enzymes in the healing of gastric ulcers in rats. World J Gastroenterol 2003;9 Suppl 8:1767-71.

Willis D, Moore AR, Willoughby DA. Hemeoxygenase isoform expression in cellular and antibody-mediated models of acute inflammation in the rat. J Pathol 2000;190:627-34.

Otterbein LE, Bach FH, Alam J, Soares M, Lu HT, Wysk M, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000;6:422-8.

Kobayashi T, Ohta Y, Inui K, Yoshino J, Nakazawa S. Protective effect of omeprazole against acute gastric mucosal lesions induced by compound 48/80, a mast cell degranulator, in rats. Pharmacol Res 2002;46:75-84.

Fornai M, Natale G, Colucci R, Tuccori M, Carazzina G, Antonioli L, et al. Mechanisms of protection by pantoprazole against NSAID-induced gastric mucosal damage. Naunyn Schmiedebergs Arch Pharmacol 2005;372:79-87.

Becker JC, Grosser N, Waltke C, Schulz S, Erdmann K, Domschke W, et al. Beyond gastric acid reduction: Proton pump inhibitors induce heme oxygenase-1 in gastric and endothelial cells. Biochem Biophys Res Commun 2006;345:1014-21.

Takagi T, Naito Y, Okada H, Ishii T, Mizushima K, Akagiri S, et al. Lansoprazole, a proton pump inhibitor, mediates anti-inflammatory effect in gastric mucosal cells through the induction of heme oxygenase-1 via activation of NF-E2-related factor 2 and oxidation of kelch-like ECH-associating protein 1. J Pharmacol Exp Ther 2009;331:255-64.

Yoda Y, Amagase K, Kato S, Tokioka S, Murano M, Kakimoto K, et al. Prevention by lansoprazole, a proton pump inhibitor, of indomethacin-induced small intestinal ulceration in rats through induction of heme oxygenase-1. J Physiol Pharmacol 2010;61:287-94.

Alrawaiq NS, Abdullah AA. Review of flavonoid quercetin: Metabolism, bioactivity and antioxidant properties. Int J PharmTech Res 2014;6:933-41.

Tanigawa S, Fujii M, Hou DX. Action of Nrf-2 and keap1 in ARE-mediated NQO1 expression by quercetin. Free Radic Biol Med 2007;42 Suppl 11:1690-703.

Garhy AM, El-Raouf OM, El-Sayeh BM, Fawzy HM, Abdallah DM. Ellagic acid anti-inflammatory and ant apoptotic potential mediate reno protection in cisplatin nephrotoxic rats. J Biochem Mol Toxicol 2014;28:472-9.

Al-Kharusi N, Babiker HA, Al-Salam S, Waly MI, Nemmar A, Al-Lawati I, et al. Ellagic acid protects against cisplatin-induced nephrotoxicity in rats: A dose-dependent study. Eur Rev Med Pharmacol Sci 2013;17 Suppl 3:299-310.

Chuian OM, Temuriants NA, Makhonina MM, Zaiachnikova TV. Effect of hypokinetic stress and low intensity electromagnetic field of extremely high frequency on changes of cytokine concentration in rat blood. Fiziol Zh 2005;51:70-8.

Kim SJ, Lee H, Lee G. CD4+CD25+ regulatory T cell depletion modulates anxiety and depression-like behaviors in mice. PLoS One 2012;7:e42054.

Padol IT, Hunt RH. Effect of Th1 cytokines on acid secretion in pharmacologically characterized mouse gastric glands. Gut 2004;53:1075-81.

Kountouras J, Boura P, Lygidakis NJ. Omeprazole and regulation of cytokine profile in Helicobacter pylori-infected patients with duodenal ulcer disease. Hepatogastroenterology 2000;47:1301-4.

Yu ES, Min HJ, Ana SY, Wona HY, Hong JH, Hwang ES. Regulatory mechanisms of IL-2 and IFNg suppression by quercetin in T helper cells. Biochem Pharm 2008;76:70-8.

Kaul S, Murphy M, Morrill J, Mathias C, Thomas D, Bose DD. Ellagic acid mediated attenuation of store operated calcium entry alters cytokine expression in Jurkat T cells. FASEB J 2016;30 Suppl 1:1138-2.

Nadatani Y, Watanabe T, Tanigawa T, Ohkawa F, Takeda S, Higashimori A, et al. High-mobility group box 1 inhibits gastric ulcer healing through toll-like receptor 4 and receptor for advanced glycation end products. PLoS One 2013;8 Suppl 11:1-13.

Li YM, Baviello G, Vlassara H, Mitsuhashi T. Glycation products in aged thioglycolate medium enhance the elicitation of peritoneal macrophages. J Immunol Methods 1997;201:183-8.

Zhao Y, Wang P, Chen H, Sang S. Dietary quercetin inhibits methylglyoxal-induced advanced glycation end products formation in mice. FASEB J 2016;30 Suppl 1:692-4.

Li X, Zheng T, Sang S, Lv L. Quercetin inhibits advanced glycation end product formation by trapping methylglyoxal and glyoxal. J Agric Food Chem 2014;62 Suppl 50:12152-8.

Muthenna P, Akileshwari C, Reddy GB. Ellagic acid, a new antiglycating agent: Its inhibition of N-(carboxymethyl) lysine. Biochem J 2012;442:221-30.

Liu W, Ma H, Frost L, Yuan T, Dain JA, Seeram NP. Pomegranate phenolics inhibit formation of advanced glycation end products by scavenging reactive carbonyl species. Food Funct 2014;5:2996-3004.

Raghu G, Jakhotia S, Reddy Y, Kumar A, Reddy GB. Ellagic acid inhibits non-enzymatic glycation and prevents proteinuria in diabetic rats. Food Funct 2016;7:1574-83.

Levitan BN, Perova NI, Astakhin AV, Trubnikov GA. Plasma fibronectin in gastric and duodenal ulcer. Klin Med (Mosk) 1999;77 Suppl 9:31-3.

Ghebremariam YT, Cooke JP, Gerhart W, Griego C, Brower JB, Doyle-Eisele M, et al. Pleiotropic effect of the proton pump inhibitor as omeprazole leading to suppression of lung inflammation and fibrosis. J Transl Med 2015;13:249-69.

Sharma A, Gupta H. Quercetin-a flavanoid. Chron Young Sci 2010;1 Suppl 1:1-6.

Mota KS, Dias GE, Pinto ME, Luiz-Ferreira Â, Souza-Brito AR, Hiruma-Lima CA, et al. Flavonoids with gastro protective activity. Molecules 2009;14:979-1012.

Sasaki S, Hirata I, Maemura K, Hamamoto N, Murano M, Toshina K, et al. Prostaglandin E2 inhibits lesion formation in dextran sodium sulphate-induced colitis in rats and reduces the levels of mucosal inflammatory cytokines. Scand J Immunol 2000;51:23-8.

Grisham MB, Granger DN. Neutrophil-mediated mucosal injury; Role of oxygen metabolites. Dig Dis Sci 1988;33:S6-S13.

Walan A, Bader JP, Classen M, Lamers C, Piper DW, Rutgersson K, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 1989;320:69-75.

Magistretti MJ, Conti M, Cristoni A. Antiulcer activity of an anthocyanidin from Vaccinium myrtillus. Arzneimittel Forschung 1988;38:686-90.

Khayyal MT, el-Ghazaly MA, Kenawy SA, Seif-el-Nasr M, Mahran LG, Kafafi YA, et al. Antiulcerogenic effect of some gastro intestinally acting plant extracts and their combination. Arzneimittel Forschung 2001;51:545-53.

Goel RK, Maiti RN, Mukobandhyay K. Effect of tamra bhasma, an Indian indigenous preparation of copper on rat gastric mucosal resistance. Indian J Exp Biol 1994;32:559-61.

Tanaka H, Kosaka N, Tomaru A, Shuto K, Oghihara T, Sato N. Augmentation of the gastric mucosal defense mechanism induced by KW - 5805, a novel antiulcer agent. Scand J Gastroenterol 1989;24:170-3.

Murakami S, Muramatsu M, Otomo S. Inhibition of gastric H+ K+-ATPase by quercetin. J Enzyme Inhib 1991;5 Suppl 4:293-8.

Murakami S, Isobe Y, Kijima H, Otomo S. Inhibition of gastric H +, K + -ATPase and acid secretion by ellagic acid. Planta Medica 1991;57 Suppl 4:305-8.

Published

01-01-2018

How to Cite

KOTOB, S. E. ., A. H. Sayed, S. H. Mohamed, and H. H. Ahmed. “QUERCETIN AND ELLAGIC ACID IN GASTRIC ULCER PREVENTION: AN INTEGRATED SCHEME OF THE POTENTIAL MECHANISMS OF ACTION FROM IN VIVO STUDY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 11, no. 1, Jan. 2018, pp. 381-9, doi:10.22159/ajpcr.2018.v11i1.21991.

Issue

Section

Original Article(s)

Most read articles by the same author(s)