ANTIULCEROGENIC EFFICACY OF ETHANOLIC EXTRACT OF VITIS VINIFERA LEAVES IN RATS

  • Dawlat A. Sayed Zoology Department, Faculty of Science, Cairo University, Egypt
  • Sohair R. Fahmy Zoology Department, Faculty of Science, Cairo University, Egypt
  • Amel M. Soliman Zoology Department, Faculty of Science, Cairo University, Egypt
  • Nagat S. Hussein Zoology Department, Faculty of Science, Cairo University, Egypt

Abstract

Objective: The ethanolic extract of Vitis vinifera leaves (VVE) (500 mg/kg body weight), ranitidine (50 mg/kg body weight) and both of them were tested for their gastroprotective and curative effects against the incidence of peptic ulcer.

Methods: The antiulcer effects of VVE were investigated using a combination of indomethacin and cold-stress for 2h. To ascertain the mechanism of action of VVE, its protective and curative effects were studied on gastric volume, gastric juice acidity, ulcer index and malondialdehyde (MDA), glutathione (GSH), catalase (CAT), glutathione–S-transferase (GST), superoxide dismutase (SOD), nitric oxide (NO) activities of both stomach and duodenum of rats. Moreover, histopathological effects on stomach and duodenum were determined.

Results: The antioxidant activity of VVE was demonstrated using 2, 2-diphenyl-1-picrylhydrazyl (DPPH) test. VVE was found to reduce the ulcer index, gastric volume and the level of gastric juice acidity. Also, VVE showed gastroprotective and curative activities mainly through improvement of antioxidant status and decreasing lipid peroxidation accompanied with amelioration of both stomach and duodenum architectures.

Conclusion: The prophylactic and curative effects of VVE proved to be effective in preventing gastric and duodenal ulceration which may be probably due to its antioxidant and anti-acid secretory effects.

Keywords: Severe gastric ulcer, Rats, Indomethacin, Cold stress, Oxidative stress

Downloads

Download data is not yet available.

References

1. Baracat F, Moura E, Bernardo W, Pu LZ, Mendonça E, Moura D, et al. Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials. Surgical Endoscopy 2016;30:2155-68.
2. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 2008; 135:41-60.
3. Ateufack G, Mokam ECD, Mbiantcha M, Feudjio RBD, David N, Kamanyi A. Gastroprotective and ulcer healing effects of piptadeniastrum Africanum on experimentally induced gastric ulcers in rats. BMC Complementary Altern Med 2015;15:214.
4. Tarnawski A, Ahluwalia A, Jones MK. Gastric cytoprotection beyond prostaglandins: cellular and molecular mechanisms of gastroprotective and ulcer healing actions of antacids. Curr Pharm Des 2013;19:126–32.
5. Hung CR. Importance of histamine, glutathione and oxyradicals in modulating gastric haemorrhagic ulcer in septic rats. Clin Exp Pharmacol Physiol 2000;27:306-12.
6. Salena BJ, Hunt RH. L’estomacet le duodénum, in Principes fond amentaux degastroentérologie: étatspathologiques et démarchesthérapeutiques. 5ème Ed. Janssen-ortho; 2005. p. 158–98.
7. Ray-Yee Yap P, Goh KL. Non-steroidal anti-inflammatory drugs (NSAIDs) induced Dyspepsia. Curr Pharm Des 2015;21:5073-81.
8. Musumba C, Pritchard DM, Pirmohamed M. Cellular and molecular mechanisms of NSAID-induced peptic ulcer. Rev Aliment Pharmacol Ther 2009;30:517-31.
9. Penney AG, Andrews FJ, O'Brien PE. Effects of misoprostol on delayed ulcer healing induced by aspirin. Dig Dis Sci 1994;39:934-9.
10. Sathyanesan M, Girgenti MJ, Warner-Schmidt J, Newton SS. Indomethacin-induced gene regulation in the rat hippocampus. Mol Brain 2015;8:59.
11. Wallace JL. Mechanisms of protection and healing: current knowledge and future research. Am J Med 2001;110 Suppl 1:S19-23.
12. Takeuchi K, Miyazawa T, Tanaka A, Kato S, Kunikata T. Pathogenic importance of intestinal hypermotility in NSAID-induced small intestinal damage in rats. Digest 2002;66:30-41.
13. Okayama T, Yoshida N, Uchiyama K, Takagi T, Ichikawa H, Yoshikawa T. Mast cells are involved in the pathogenesis of indomethacin-induced rat enteritis. J Gastroenterol 2009;44:35-9.
14. Dharmani P, Kuchibhotla VK, Maurya R, Srivastava S, Sharma S, Palit G. Evaluation of anti‐ulcerogenic and ulcer‐healing properties of Ocimum sanctum Linn. J Ethnopharmacol 2004;93:197–206.
15. Fahmy SR, Amer MA, Al-killidar MH. Ameliorative effect of the sea cucumber Holothuriaarenicola extracts against gastric ulcer in rats. J Basic Appl Zool 2015;72:16-25.
16. Chandra K, Salman AS, Mohd A, Sweety R, Ali KN. Protection against FCA induced oxidative stress-induced DNA damage as a model of arthritis and in vitro anti-arthritic potential of costus specious rhizome extract. J Pharm Phytochem Res 2015;7:383-9.
17. Uduak EU, Timbuak JA, Musa SA, Ikyembe DT, Abdurrashid S, Hamman WO. Ulceroprotective effect of methanol extract of Psidium guajava leaves on an ethanol-induced gastric ulcer in adult wistar rats. Asian J Med Sci 2012;4:75-8.
18. Shanthi A, Radha R, Jaysree N. Anti-ulcer activity of newly formulated herbal capsule. Asian J Pharm Clin Res 2011;4:86-9.
19. Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, et al. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals.
Saudi J Gastroenterol 2008;14:128–34.
20. Bourdet DL, Pritchard JB, Thakker DR. Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1;SLC22A1), hOCTt2 (SLC22A2), and hOCT3 (SLC22A3). J Pharmacol Exp Ther 2005;315:1288-97.
21. Banji D, Singh J, Banji OJ. Scrutinizing the aqueous extract of leaves of pedalium murex for the antiulcer activity in rats. Pak J Pharm Sci 2010;23:295-9.
22. Alkofahi A, Atta AH. Pharmacological screening of the antiulcerogenic effects of some Jordanian medicinal plants in rats. J Ethnopharmacol 1999;67:341–5.
23. Schmeda Hirschmann G, Yesilada E. Traditional medicine and gastroprotective crude drugs. J Ethnopharmacol 2005;100:61-6.
24. Jayaprakasha GK, Selvi T, Sakariah KK. Antibacterial and antioxidant activities of grape (Vitisvinifera) seed extracts. Food Res Int 2003;36:117-22.
25. Orallo F. Trans-resveratrol: a magical elixir of eternal youth? Curr Med Chem 2008;15:1887-98.
26. Asl MN, Hosseinzadeh H. Review of the pharmacological effects of Vitis vinifera (grape) and its bioactive compounds. Phytother Res 2009;23:1197–204.
27. Ali K, Maltese F, Choi YH, Verpoorte R. Metabolic constituents of grapevine and grape-derived products. Phytochem Rev 2010;9:357-78.
28. Tsao R. Chemistry and biochemistry of dietary polyphenols. Nutrition 2010;2:1231-46.
29. Pastrana-Bonilla E, Akoh CC, Sellappan S, Krewer G. Phenolic content and antioxidant capacity of muscadine grapes. J Agric Food Chem 2003;51:5497-503.
30. Seo DJ, Lee HB, Kim IS, Kim KY, Park RD, Jung WJ. Antifungal activity of gallic acid purified from Terminalia Nigro venulose bark against Fusarium solani. Microb Pathog 2013;56:8-15.
31. Rather SA, Sarumathi A, Anbu S, Saravanan N. Gallic acid protects against immobilization stress-induced changes in wistar rats. J Stress Physiol Biochem 2013;9:136-47.
32. Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 1995;28:25-30.
33. Trease GE, Evans WC. Pharmacognosy. 15th Ed. London: Saunders Publishers; 2002.
34. Parekh J, Chanda S. In vitro screening of antibacterial activity of aqueous and alcoholic extracts of various Indian plant species against selected pathogens from Enterobacteriaceae. Afr J Microbiol Res 2007;1:92-9.
35. Ayoola GA, Ipav SS, Sofidiya MO, Adepoju-Bello AA, Coker HA, Odugbemi TO. Phytochemical screening and free radical scavenging activities of the fruits and leaves of Allanblackia floribunda Oliv (Guttiferae). Int J Health Res 2008;1:87-93.
36. Kodangala C, Saha S, Kodangala P. Phytochemical studies of aerial parts of the plant Leucaslavandulaefolia. Scholars Res Library Der Pharm Chem 2010;2:434-7.
37. Vanden Heuvel MJ, Clark DG, Fielder RJ, Koundakjian PP, Oliver GJA, Pelling D, et al. The international validation of a fixed-dose procedure as an alternative to the classical LD50 test. Food Chem Toxicol 1999;28:469–82.
38. Whitehead A, Curnow RN. Statistica evaluation of the fixed dose procedure. Food Chem Toxicol 1992;30:313–24.
39. Arai I, Hirose H, Usuki C, Muramatsu M, Aihara H. Effects of indomethacin and cold stress on gastric acid secreation and ulceration. The effect of anti acid secretory agents in rats. Res Commun Chem Pathol Pharmacol 1987;57:313-27.
40. Thong-Ngam D, Choochuai S, Patumraj S, Chayanupatkul M, Klaikeaw N. Curcumin prevents indomethacin-induced gastropathy in rats. World J Gastroenterol 2010;18: 1479-84.
41. Jeong Hwan K, Kim B, Kwon H, Nam S. Curative effect of selenium against indomethacin-induced gastric ulcers in rats. J Microbiol Biotechnol 2011;21:400–4.
42. Nguelefack TB, Feumebo CB, Ateufack G, Watcho P, Tatsimo S, Atsamo AD, et al. Antiulcerogenic properties of the aqueous and methanol extracts of leaves of Solanum torvum Swartz (Solanaceae) in rats. J Ethnopharmacol 2008;119:135‐40.
43. Parmar NS, Desai JK. A review of the current methodology for the evaluation of gastric and duodenal anti-ulcer agents. Indian J Pharmacol 1993;25:120-35.
44. Kulkarni SK. Handbook of experimental pharmacology. 3rded. New Delhi: Vallabh; 2010.
45. Dashputre NL, Naikwade NS. Evaluation of the anti-ulcer activity of methanolic extract of Abutilon indicum Linn leaves in experimental rats. Int J Pharm Sci Drug Res 2011;3:97-100.
46. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
47. Aykac J, Uysal M, Yalcin A, Kocak Toke N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione peroxidase and glutathione transferase in rats. Toxicology 1985;36:71-6.
48. Montgomery HAC, Dymock JF. Colorimetric determination of nitrite. Analyst 1961;86:414-6.
49. Aebi H. Catalase in vitro. Methods Enzymol 1948;105:121-6.
50. Habig W, Pabst M, Jakpby W. Glutathione s-transferases the first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-9.
51. Nishikimi M, Roa NA, Yogi K. The occurrence of the superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem Biophys Res Commun 1972;46:849-85.
52. Ozbayer C, Kurt H, Ozdemir Z, Tuncel T, Moheb Saadat S, Burukoglu D, et al. Gastroprotective, cytoprotective and antioxidant effects of Oleum cinnamomi on ethanol-induced damage. Cytotechnology 2014;66:431-41.
53. Choudhary M, Kumar V, Singh S. Gastric antisecretory and cytoprotective effects of hydroalcoholic extracts of PlumeriaalbaLinn. Leaves in rats. J Integr Med 2014;12:42–51.
54. Kim JH, Chol SK, Lim WJ, Chang HI. Protective effect of astaxanthin produced by Xantho-phyllomycesden dro rho us mutant on indomethacin-induced gastric mucosal injury in rats. J Microbiol Biotechnol 2004;14:996-1003.
55. Tiwari DK, Tripathi RK, Jena J. Evaluation of antiulcer and antianxiety activity of Aphanamixispolystachya stems bark extract on rats. Int J Pharm Pharm Sci 2013;5:148–51.
56. Harvey AL, Edrada-Ebel R, Quinn RJ. The re-emergence of natural products for drug discovery in the genomics era. Nat Rev Drug Discovery 2015;14:111-29.
57. Kumarasamy Y, Byres M, Cox PJ, Jaspars M, Nahar L, Sarker SD. Screening seeds of some scottish plants for free-radical scavenging activity. Phytotherapy Res 2007;21:615-21.
58. Nagar H, Tiwari P, Jain DK, Chandel HS. Evaluation of the anti-ulcer activity of stem bark extract of Aphanmixis polystachya in experimental rats. Indian J Pharm Educ Res 2012;46:222-7.
59. Bighetti AE, Antonio MA, Kohn LK, Rehder VLG, Foglio MA, Possenti A, et al. the Antiulcerogenic activity of a crude hydroalcoholic extract and coumarin isolated from mikanialaevigata schultz bip. Phytomedicine 2005;12:72-7.
60. John-Africa BL, Idris-Usman MS, Adzu B, Gamaniel KS. Protective effects of the aqueous extract of Nymphaea lotus L. (Nymphaeaceae) against ethanol-induced gastric ulcers. Int J Biol Chem Sci 2012;6:1917-25.
61. Bhattacharya S, Chatterjee S, Bauri A, Bandivdeker AH, Chattopadhyay S, Bandyopadhyay SK, et al. Immunopharmacological basis of the healing of indomethacin-induced gastric mucosal damage in rats by the constituents of phyllanthusemblica. Curr Sci 2007;93:47-55.
62. Pal C, Bindu S, Dey S, Alam A, Goyal M, Iqbal MS, et al. Gallic acid prevents nonsteroidal anti-inflammatory drug-induced gastropathy in the rat by blocking oxidative stress and apoptosis. Free Radicals Biol Med 2010;49:258-67.
63. Mei XT, Xu DH, Xu SK, Zheng YP, Xu SB. Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9. Food Chem Toxicol 2013;60:448–54.
64. Ajeigbe K, Oladejo E, Emikpe B, Asuk A, Olaleye S. The dual modulatory effect of folic acid supplementation on indomethacin-induced gastropathy in the rat. Turk J Gastroenterol 2012;23:639–45.
65. Abbas Am, Sakr HF. Effect of selenium and grape seed extract on indomethacin–induced gastric ulcers in rats. J Physiol Biochem 2013;69:527-73.
66. Pérez Y, Oyárzabal A, Mas R, Molina V, Jiménez S. Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action. J Nat Med 2013;67:182–9.
67. Vemula SK, Chawada MB, Thakur KS, Vahalia MK. Antiulcer activity of Amlapitta mishran suspension in rats: a pilot study. Ancient Sci Life 2012;32:112–5.
68. ÅžendoÄŸdu N, Aslan M, Orhand D, Ergun F, Yesllada E. Antidiabetic and antioxidant effects of Vitis vinifera L. leaves in streptozotocin-diabetic rats. Turkish J Pharm Sci 2006;3:7-18.
69. de Lira Mota KS, Dias GEN, Pinto MEF, Luiz-Ferreira Â, Monteiro Souza-Brito AR, Hiruma-Lima CA, et al. Flavonoids with gastroprotective activity. Molecules 2009;14:979-1012.
70. Pushpakiran G, Mahalakshmi K, Anuradha CV. Protective effects of taurine on glutathione and glutathione-dependent enzymes in ethanol-fed rats. Pharmazie 2004;59:869-72.
71. Lii CK, Ko YJ, Chiang MT, Sung WC, Chen HW. Effect of dietary vitamin E on antioxidant status and antioxidant enzyme activities in sprague‐dawley rats. Nutr Cancer 1992;32:95-100.
72. Nartey ET, Ofosuhene, Agbale cM. The anti-ulcerogenic activity of the root bark extract of the African laburnum‘‘ cassia sieberiana‘‘ and its effect on the antioxidant defense system in rats. BMC Complementary Altern Med 2012;10:247.
73. Radovanović TB, Borković-Mitić SS, Perendija BR, Despotović SG, Pavlović SZ, Cakić PD, et al. Superoxide dismutase and catalase activities in the liver and muscle of barbel (Barbusbarbus) and its intestinal parasite (Pomphoryinchuslaevis) from the danube river, Serbia. Arch Biol Sci 2010;62:97-105.
74. Halliwell B, Gutteridge JM. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984;219:1-14.
75. Khan MS, Khan MK, Siddiqui MH, Arif JM. An in vivo and in silico approach to elucidate the tocotrienol-mediated fortification against infection and inflammation induced alterations in antioxidant defense system. Eur Rev Med Pharmacol Sci 2011;15:916-30.
76. Halici M, Odabasoglu F, Suleyman H, Cakir A, Aslan A, Bayir Y. Effect’s of water extract of Usnealongissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats. Phytomedicine 2005;12:656–62.
77. Bayir Y, Odabasoglu F, Cakir A, Aslan A, Suleyman H, Halici M, et al. The inhibition of gastric mucosal lesion, oxidative stress and neutrophil infiltration in rats by the lichen constituent diffractaic acid. Phytomedicine 2006;13:584-90.
78. Odabasoglu F, Cakir A, Suleyman H, Aslan A, Bayir Y, Halici M, et al. Gastroprotective and antioxidant effects of usnic acid on indomethacin-induced gastric ulcer in rats. J Ethnopharmacol 2006;103:59-65.
79. Zelko IN, Mariani TJ, Folz RJ. Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radical Biol Med 2002;33:337-49.
80. Heeba GH, Hassan MK, Amin RS. Gastroprotective effect of simvastatin against indomethacin-induced gastric ulcer in rats: the role of nitric oxide and prostaglandins. Eur J Pharmacol 2009;607:188-93.
81. Badr GM, AL-Mulhim JA. The protective effect of aged garlic extract on nonsteroidal anti-inflammatory drug-induced gastric inflammations in male albino rats. J Evidence Based Complementary Altern Med 2014. Doi:10.1155/2014/759642.
82. Torres MA, Testa CP, Gaspari C, Masutti MB, Panitz CMN, Curi-Pedrosa R, et al. Oxidative stress in the mussel Mytellaguyanensis from polluted mangroves on Santa Catarina Island, Brazil. Mar Pollut Bull 2002;44:923–32.
83. Fernandes F, Ramalhosa E, Pires P, Verdial J, Valentão P, Andrade P, et al. Vitis vinifera leaves towards bioactivity. Ind Crops Prod 2013;43:434-40.
84. Samini M, Moezi L, Jabarizadeh N, Tavakolifar B, Shafaroodi H, Dehpour AR. Evidence for the involvement of nitric oxide in the gastroprotective effect of bromocriptine and cyclosporin A on water immersion stress-induced gastric lesions. Pharm Res 2002;46:519-23.
85. Holzer P. Neural regulation of gastrointestinal blood flow. In: Physiology of the gastrointestinal tract. LR Johnson. 4th Ed. Academic Press: New York, EUA; 2006. p. 817-39.
86. Slomiany BL, Slomiany A. Role of endothelin converting enzyme-1 in the suppression of constitutive nitric oxide synthase in rat gastric mucosal injury by indomethacin. Scand J Gastroenterol 2000;35:1131-6.
87. Matsuda H, Morikawa T, Ando S, Toguchida I, Yoshikawa M. Structural requirements of flavonoids for nitric oxide production inhibitory activity and mechanism of action. Bioorg Med Chem 2003;11:1995-2000.
88. Elegbe RA. Comparative studies on starvation and indomethacin–induced ulceration in albino rats. Biochem Exp Biol 1978;14:158-66.
89. Olaleye SB, Ajeigbe KO. Attenuation of experimental gasric ulceration by sulfadoxine-pyrimethamine in albino Rats. J Med Sci 2009;9:87–92.
90. Robert A, Nezamis JE, Lancaster C, Hanchar AJ. Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterol 1979;77:433-43.
91. Olaleye SB, Farombi EO. Attenuation of Indomethacin and HCl/Ethanol-induced oxidative gastric mucosa damage in rats by kolaviron (Garcinia bi flavanones). Phytother Res 2006;20:14-20.
92. Devi SA, Chandrasekar BS, Manjula KR, Ishii N. Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Exp Gerontol 2011;46:958-64.
Statistics
493 Views | 1593 Downloads
How to Cite
Sayed, D. A., S. R. Fahmy, A. M. Soliman, and N. S. Hussein. “ANTIULCEROGENIC EFFICACY OF ETHANOLIC EXTRACT OF VITIS VINIFERA LEAVES IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 9, Sept. 2016, p. 163-72, doi:10.22159/ijpps.2016v8i9.12846.
Section
Original Article(s)