title: Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation.
abstract: The mechanism of indomethacin-induced gastric ulcer healing by ellagic acid (EA) in experimental mice model is described in our study. Ulcer index (UI) and myeloperoxidase (MPO) activity of the stomach tissues showed maximum ulceration on the third day after indomethacin (18 mg/kg, single dose) administration. Preliminary observation of UI and MPO activity suggests that EA possesses ulcer-healing activity. Other anti-ulcer parameters such as the levels of prostaglandin E(2), cyclooxygenase (COX) 1 and 2 enzymes, anti-inflammatory cytokines [interleukin (IL)-4 and -5], pro-angiogenic factors, e.g. vascular endothelial growth factor, hepatocyte growth factor (HGF), and endothelial growth factor (EGF) were down-regulated by indomethacin. EA (7 mg/kg/day) treatment for 3 days shifted the indomethacin-induced pro-inflammatory biochemical parameters to the healing side. These activities were correlated with the ability of EA to alter the COX-2-dependent healing pathways. The ulcer-healing activity of EA was, however, compromised by pre-administration of the specific COX-2 inhibitor, celecoxib, and NS-398. Taken together, these results suggested that the EA treatment accelerates ulcer healing by inducing IL-4, EGF/HGF levels and enhances COX-2 expression.
authors.affiliation: Department of Biochemistry, University College of Medicine, I.P.G.M.E&R, West Bengal, India.
authors.forename: Ananya
authors.initials: A
authors.lastname: Chatterjee
authors.forename: Sirshendu
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Smita
authors.initials: S
authors.lastname: Das
authors.forename: Arpita
authors.initials: A
authors.lastname: Saha
authors.forename: Subrata
authors.initials: S
authors.lastname: Chattopadhyay
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Bandyopadhyay
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000068579:Celecoxib; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004610:Ellagic Acid / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009578:Nitrobenzenes / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D009578:Nitrobenzenes; D011720:Pyrazoles; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004610:Ellagic Acid; D009195:Peroxidase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D015232:Dinoprostone; D007213:Indomethacin