GASTRIC ANTIULCER AND ULCER HEALING EFFECTS OF PUNICA GRANATUM L. PEEL EXTRACT IN RATS: ROLE OF OFFENSIVE AND DEFENSIVE MUCOSAL FACTORS AND OXIDATIVE STRESS
DOI:
https://doi.org/10.22159/ijpps.2017v9i5.9851Keywords:
Punica granatum peel, Gastric ulcer, Mucosal defence, Free radicals, AntioxidantsAbstract
Objective: The present work incorporates the study of gastric antiulcer and ulcer healing effects of dried Punica granatum (PG) peel 50% ethanol extract (PGE) in rats.
Methods: PGE (100 mg/kg) was administered orally once daily to rats either before or after induction of gastric ulcers (GU) for 7 d. Antiulcer effects of PGE were seen against acute GU, induced by pylorus ligation (PL), cold restraint stress (CRS), aspirin and ethanol while, ulcer healing in acetic acid (AA)-induced chronic GU in rats. Ulcer index (UI), gastric juice volume, acid-pepsin and mucin secretions and gastric mucosal glycoproteins, free radicals (LPO and NO) and antioxidants (SOD and GSH) were estimated.
Results: PGE showed a decrease in UI in all GU models (45.6 to 79.7%, P<0.05 to P<0.001) indicating both protective and healing effects. PGE showed little or no effects on volume, acid-pepsin concentration and output but increased mucin secretion (55.1%, P<0.05) and mucosal glycoproteins (35.7%, P<0.05) in PL rats. CRS rats showed an increase in LPO and NO (48.4 to 58.3%, P<0.01) and SOD (21.8%, P<0.01) but decrease in GSH and CAT (33.1 to 44.8%, P<0.01 to P<0.001) compared with unstressed rats. PGE-treated CRS rats showed a decrease in LPO and NO (44.1 to 61.2, P<0.01 to P<0.001) and SOD (13.2%, P<0.01) and increase in GSH and CAT (43.8 to 48.7%, P<0.01 to P<0.001) compared with CRS rats.
Conclusion: PGE seemed to have ulcer cytoprotective effects due to enhanced mucosal resistance and reduction in oxidative mucosal damage possibly via high antioxidant activity.
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References
Goel RK, Bhattacharya SK. Gastroduodenal mucosal defence and mucosal protective agents. Indian J Exp Biol 1991;29:701-14.
Patil VP, Viswanathswamy AHM, Kamblekar YJ, Hallikeri CS, Hatapakki BC. Gastroprotective and anti-ulcer properties of clozapine in pylorus ligated rats. Int J Pharmacol Biol Sci 2008;2:121-7.
Mohan Kumar M, Joshi MC, Prabha T, Dorababu M, Goel RK. Effect of plantain banana on gastric ulceration in NIDDM rats: the role of mucosal glycoproteins, cell proliferation, antioxidants and free radical. Indian J Exp Biol 2006;44:292-9.
Mózsik G. Gastric cytoprotection 30 y after its discovery by André Robert: a personal perspective. Inflammopharmacology 2010;18:209-21.
Rosa S, D’Souza D, Dhume VG. Gastric cytoprotection. Indian J Physiol Pharmacol 1991;35:88-98.
Garachh D, Patel A, Chakraborty M, Kamath JV. Phytochemical and pharmacological profile of Punica granatum. Int Res J Pharm 2012;3:65-8.
Bhandari PR. Pomegranate (Punica granatum L). Ancient seeds for modern cure? Review of potential therapeutic applications. Int J Nutr Pharmacol Neurol Dis 2012;2:171-84.
Alam MS, Alam MA, Ahmad S, Nazmi AK, Asif M, Jahangir T. Protective effects of Punica granatum in experimentally-induced gastric ulcers. Toxicol Mech Methods 2010;20:572-8.
Gautam R, Sharma SC. Anti-ulcer activity of Punica granatum Linn in diabetic rats. Int J Pharm Pharm Sci 2012;4(Suppl 3):459-61.
Moghaddam G, Sharifzadeh M, Hassanzadeh G, Khanavi M, Hazimahmoodi M. Antiulcerogenic activity of the pomegranate peel (Punica granatum) methanol extract. Food Nutr Sci 2013;4:1-7.
Bakhtaoui Fatima-Zahra, Lakmichi H, Chait A, Gadhi CA. In vivo gastroprotective effects of five Moroccan Medicinal plants against gastric ulcer. Am J Phytomed Clin Ther 2014;2:1262-76.
Lai S, Zhou Q, Zhang Y, Shang J, Yu T. Effects of pomegranate tannins on experimental gastric damages. Zhongguo Zhong Yao Zazhi 2009;34:1290-4.
Haque N, Sofi G, Ali W, Rashid M, Itrat MA. Comparative review of phytochemical and pharmacological profile of Anar (Punica granatum Linn): a heaven’s fruit. J Ayu Herb Med 2015;1:22-6.
Prabha T, Dorababu M, Goel Shalini, Agarwal PK, Singh A, Joshi VK, Goel RK. Effect of methanolic extract of Pongamia pinnata Linn seed on gastroduodenal ulceration and mucosal offensive and defensive factors in rats. Indian J Exp Biol 2009;47:649-59.
Sanyal AK., Pandey BL, Goel RK. The effect of a traditional preparation of copper, tamrabhasma, on experimental ulcers and gastric secretion. J Ethnopharmacol 1982;5:79-89.
Goel RK, Govinda Das D, Sanyal AK. Effect of vegetable banana powder on changes induced by ulcerogenic agents on dissolved mucosubstances in gastric juice. Indian J Gastroenterol 1985;4:249-51.
Hollander D, Tarnawski A, Kruse WJ, Gergley H. Protective effect of sucralfate against alcohol-induced gastric mucosal injury in the rat. Gastroenterol 1985;88:366-74.
Goel RK, Maiti RN. Gastric ulcer protective effect of Tamrabhasma, an Indian Ayurvedic preparation of copper and plantain banana. Proceedings of First International Symposium on Natural Drugs and the Digestive tract, Naples Italy; 1992. p. 73-6.
Sanyal AK, Debnath PK, Bhattacharya SK, Gode KD. The effect of cyproheptadine on gastric activity. An experimental study. In: Pfeiffer CJ editor. Peptic Ulcer, Munksgaard, Copenhagen; 1971. p. 312-8.
Debnath PK, Gode KD, Govinda Das D, Sanyal AK. Effect of propranolol on gastric secretion in albino rats. Br J Pharmacol 1974;51:213-6.
Winzler RJ. Determination of serum glycoproteins. Methods Biochem Anal 1958;2:279-311.
Dische Z, Borenfreund e. a spectroscopic method for the micro determination of hexosamine. J Biol Chem 1950;184:517-22.
Dische Z, Shettles LB. A specific colour reaction for methyl pentoses and spectrophotometric micro method for their determination. J Biol Chem 1948;175:595-603.
Warren L. The thiobarbituric acid assay of sialic acid. J Biol Chem 1959;234:1971-5.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951;193:265-75.
Sanyal AK, Mitra PK, Goel RK. A modified method to estimate dissolved mucosubstances in gastric juice. Indian J Exp Biol 1983;21:78-80.
Goel RK, Gupta Saroj, Shankar R, Sanyal AK. Anti-ulcerogenic effect of banana powder Musa sapientum var. paradisiaca) and its effects on mucosal resistance. J Ethnopharmacol 1986;18:33-44.
Okhawa H Ohishi N, Yagi K. Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 2001;5:62-71.
Aebi H. Catalase. In: Bergmeyer HU. editor. Methods in enzymatic analysis. Vol. 3 (2nd Ed.) New York: Academic Press; 1974. p. 673-7.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130-2.
Sedlak J, Lindsay RH. Estimation of total, protein-bound and non-protein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 1968;25:192-205.
Bandyopadhyay D, Chattopadhyay A. Reactive oxygen species-induced gastric ulceration: protection by melatonin. Curr Med Chem 2006;13:1187-202.
Goel RK, Tavares IA, Bennett A. Effect of ethanol on eicosanoid synthesis by human gastric and colonic mucosal pieces. Br J Pharmacol 1990;99:289-92.
Okabe S, Amagase K. An overview of acetic acid ulcer models-the history and state of the art of peptic ulcer research. Biol Pharm Bull 2005;28:1321-41.
Goel RK, Maiti RN, Mukhopadhyaya K. Effect of Tamrabhasma, an indigenous Indian preparation of copper, on rat gastric mucosal resistance. Indian J Exp Biol 1994;32:559-61.
Wallace JL. Increased resistance of the rat gastric mucosa to hemorrhagic damage after exposure to an irritant: the role of the mucoid cap†and prostaglandin synthesis. Gastroenterology 1988;94:22-32.
Fridovich I. Biological effects of superoxide radical. Arch Biochem Biophys 1986;247:1-11.
Del Maestro R, Thaw HH, Bjork J, Planker M, Arfors KE. Free radicals as mediators of tissue injury. Acta Physiol Scand 1980;Suppl 492:43-57.
Lopez-Belmonte J, Whittle BJR. The involvement of endothelial dysfunction, nitric oxide and prostanoids in the rat gastric microcirculatory responses to endothelin-1. Br J Pharmacol 1994;112:267-71.
Mourelle M, Vilaseca J, Guarner F, Salas A, Malagelada JR. Toxic dilation of the colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase. Am J Physiol 1996;270:G425-30.
Kumaraguruparan R, Subapriya R, Viswanathan P, Nagini S. Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast. Clin Chim Acta 2002;325:165-70.