Ellagic acid facilitates indomethacin-induced gastric ulcer healing via COX-2 up-regulation

The mechanism of indomethacin-induced gastric ulcer healing by eUagic acid （EA） in experimental mice model is described in our study. Ulcer index （UI） and myeloperoxi- dase （MPO） activity of the stomach tissues showed maximum ulceration on the third day after indomethacin （18 mg/kg, single dose） administration. Preliminary obser- vation of UI and MPO activity suggests that EA possesses ulcer-healing activity. Other anti-ulcer parameters such as the levels of prostaglandin E~, cyclooxygenase （COX） 1 and 2 enzymes, anti-inflammatory cytokines [interleukin （IL）-4 and -5｜, pro-angiogenic factors, e.g. vascular endo- thelial 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 bio- chemical 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 treat- ment accelerates ulcer healing by inducing IL-4, EGF/ HGF levels and enhances COX-2 expression.