Meltem KOLGAZİ, Gulsen OZTOSUN, Muge YALCIN, Zehra Neslisah UNAN, Edanur ARSOY, Simge ORAL, Sumeyye CILINGIR, Merve Açıkel ELMAS, Serap ARBAK

p-Coumaric acid has an ameliorative effect on peptic ulcer: a macroscopic, microscopic and biochemical analysis

Objective: p-Coumaric acid is commonly found in edible plants in nature and is known to be an effective antioxidant. This study aimed to investigate the therapeutic effects of p-coumaric acid on ethanol-induced gastric ulcer model Materials and Methods: After an 18-hour starvation period, the ulcer was induced in male Sprague-Dawley (250-300) rats by intragastric administration of 75% ethanol. An hour after ulcer induction, p-coumaric acid (250 mg/kg) suspended in 1 ml tween-80 was administered intragastrically. The control and ulcer groups received 1 ml tween-80. One hour later, all rats were euthanized and stomach samples were collected for macroscopic examination, histological evaluation, and measurement of myeloperoxidase (MPO) activity, malondialdehyde (MDA), and glutathione (GSH) levels. Results: Ethanol induction resulted in gastric epithelial and mucosal injury, increased MPO activity and MDA levels; and decreased GSH levels. Treatment with p-coumaric acid at a dose of 250 mg/kg markedly improved the gastric injury macroscopically, microscopically, and biochemically due to decreasing MPO activity and MDA levels while increasing GSH levels. Conclusion: p-Coumaric acid markedly ameliorated the gastric epithelial and mucosal injury induced by ethanol. The therapeutic effects of p-coumaric acid could be due to its antioxidant properties and protective role against GSH depletion and neutrophil accumulation.

Keywords:

p-Coumaric acid, Ulcer, Ethanol, Antioxidant, Neutrophil,

PDF

___

dietary sources, pharmacokinetic properties and biological activities. J Sci Food Agric 2015; 96:2952-62. doi: 10.1002/ jsfa.7578
Goleniowski M, Bonfill M, Cusido RM, Palazon J. Phenolic Acids. Natural Products. 2013 Springer-Verlag Berlin Heidelberg:1951–1973. doi: 10.1007/978-3-642-22144-6_64
Sakamula R, Thong-Asa W. Neuroprotective effect of p-coumaric acid in mice with cerebral ischemia reperfusion injuries. Metab Brain Dis 2018; 33:765-73. doi: 10.1007/ s11011.018.0185-7
Zang LY, Cosma G, Gardner H, Shi X, Castranova V, Vallyathan V. Effect of antioxidant protection by p-coumaric acid on low-density lipoprotein cholesterol oxidation. Am J Physiol Cell Physiol 2000; 279:C954-60. doi: 10.1152/ ajpcell.2000.279.4.C954
Ragab SM, AbdElghaffar SK, El-Metwally TH, Badr G, Mahmoud MH, Omar HM. Effect of a high fat, high sucrose diet on the promotion of non-alcoholic fatty liver disease in male rats: the ameliorative role of three natural compounds. Lipids Health Dis 2015; 14: 83. doi: 10.1186/s12944.015.0087-1
Loo G. Redox-sensitive mechanisms of phytochemicalmediated inhibition of cancer cell proliferation. J Nutr Biochem 2003; 14:64-73. doi: 10.1016/S0955-2863(02)00251-6
Sharma SH, Rajamanickam V, Nagarajan S. Antiproliferative effect of p-Coumaric acid targets UPR activation by downregulating Grp78 in colon cancer. ChemBiol Interact 2018; 291:16-28. doi: 10.1016/j.cbi/2018.06.001
Pragasam SJ, Venkatesan V, Rasool M. Immunomodulatory and anti-inflammatory effect of p-coumaric acid, a common dietary polyphenol on experimental inflammation in rats. Inflammation 2013; 36:169-176. doi: 10.1007/ s10753.012.9532-8
Neog MK, PragasamSJ, Krishnan M, Rasool M. p‐Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails cartilage and bone erosion in the rheumatoid arthritis rat model. Biofactors 2017; 43:698-717. doi: 10.1002/biof.1377
Kilani-Jaziri S, Mokdad-Bzeouich I, Krifa M, Nasr N, Ghedira K, Chekir-Ghedira L. Immunomodulatory and cellular antioxidant activities of caffeic, ferulic, and p-coumaric phenolic acids: a structure-activity relationship study. Drug ChemToxicol 2017; 40:416-24. doi: 10.1080/01480.545.2016.1252919
Thorsen K, Søreide JA, Kvaløy JT, Glomsaker T, Søreide K. Epidemiology of perforated peptic ulcer: Age – and gender-adjusted analysis of incidence and mortality. World J Gastroenterol 2013; 19:347-54. doi: 10.3748/wjg.v109.i3.347
Salena BJ, Hunt RH. The stomach and duodenum. First Principles of Gastroenterology: the Basis of Disease and an Approach to Management. Mississauga, Canada: Canadian Association of Gastroenterology/Astra Pharmaceuticals, 1994:135-181.
Adinortey MB, Ansah C, Galyuon I, Nyarko A. In Vivo models used for evaluation of potential antigastroduodenal ulcer agents. Ulcers 2013; 2013:1-12. doi: 10.1155/2013/796405
Shen Y, Sun J, Niu C, et al. Mechanistic evaluation of gastroprotective effects of Kangfuxin on ethanol-induced gastric ulcer in mice. Chem Biol Interact 2017; 273:115-24. doi: 10.1016/j.cbi.2017.06.007
Kwiecień S, Brzozowski T, Konturek SJ. Effects of reactive oxygen species action on gastric mucosa in various models of mucosal injury. J Physiol Pharmacol 2002; 53:39-50. PMID: 11939718
Barros MP, Lemos M, Maistro EL, et al. Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis. J Ethnopharmacol 2008; 120:372-7. doi: 10.1016/j. jep.2008.09.015
Szabo S, Trier JS, Brown A, Schnoor J, Homan HD, Bradford JC. A quantitative method for assessing the extent of experimental gastric erosions and ulcers. J Pharmacol Methods 1985; 13:59- 66. doi: 10.1016/0160-5402(85)90068-3
Jahovic N, Erkanli G, Işeri S, Arbak S, Alican I. Gastric protection by alpha-melanocyte-stimulating hormone against ethanol in rats: involvement of somatostatin. Life Sci 2007; 80:1040-5. doi: 10.1016/j.lfs.2006.11.036
Casini A, Ferrali M, Pompella AS, Maellaro E, Comporti M. Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am. J. Pathol 1986; 123:520-31.
Aykac G, Uysal M, Yalcin AS, Kocak-Toker N, Sivas A, Oz H. The effect of chronic ethanol ingestion on hepatic lipidperoxide, glutathione peroxidase and glutathione transferase in rat. Toxicology 1985; 46:71-6. doi: 10.1016/0300- 483X(85)90008-3
Bradley PP, Preibat D, Christerser RD, Rothstein G. Measurement of cutaneous inflammation, estimation of neutrophil content with an enzyme marker. J. Invest. Dermatol 1982; 78:206-9. doi: 0022-202X/82/7803-0206$02.00/0
Vomero ND, Colpo E. Nutritional care in peptic ulcer. Arq Bras Cir Dig 2014; 27:298–302. doi: 10.1590/ S0102.672.0201400.040.0017
Alam MA, Subhan N, Hossain H, et al. Hydroxycinnamic acid derivatives: a potential class of natural compounds for the management of lipid metabolism and obesity. Nutr Metab (Lond) 2016; 13:27. doi: 10.1186/s12986.016.0080-3
Kiliç I, Yeşiloğlu Y. Spectroscopic studies on the antioxidant activity of p-coumaric acid. Spectrochim Acta A Mol Biomol Spectrosc 2013; 115:719-24. doi: 10.1016/j.saa.2013.06.110
Liu Y, Tian X, Gou L, et al. Protective effect of l-citrulline against ethanol-induced gastric ulcer in rats. Environ Toxicol Pharmacol 2012; 34:280-7. doi: 10.1016/j.etap.2012.04.009
Brzozowski T, Konturek PC, Konturek SJ, et al. The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia, and aspirin. J. Pineal Res 1997; 23:79-89. doi: 10.1111/j.1600.079X.1997. tb00339.x
Wright HL, Moots RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory diseases. Rheumatology (Oxford) 2010; 49:1618-31. doi: 10.1093/ rheumatology/keq045
Bhattacharyya A, Chattopadhyay R, Mitra S, Crowe SE. Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 2014; 94:329- 54. doi: 10.1152/physrev.00040.2012
Kolgazi M, Cantali-Ozturk C, Deniz R, et al. Nesfatin-1 alleviates gastric damage via direct antioxidant mechanisms. J Surg Res 2015; 193:111-8. doi: 10.1016/j.jss.2014.06.057
Chen SH, Liang YC, Chao JC, et al. Protective effects of Ginkgo biloba extract on the ethanol-induced gastric ulcer in rats. World J Gastroenterol 2005; 11:3746-50. doi: 10.3748/ wjg.v11.i24.3746
EkinciAkdemir FN, Albayrak M, Çalik M, Bayir Y, Gülçin İ. The protective effects of p-coumaric acid on acute liver and kidney damages induced by cisplatin. Biomedicines 2017; 28;5 (2):18. doi: 10.3390/biomedicines5020018
Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010; 4:118-26. doi: 10.4103/0973- 7847.70902