Protective effect of chrysin on indomethacin induced gastric ulcer in rats: role of multi-pathway regulation.

We investigated the potential gastroprotective effects of chrysin on indomethacin induced gastric ulcers in rats. We used six groups of animals: control; indomethacin (Indo); reference (Ulcuran®); indomethacin + 25 mg/kg chrysin (Indo + CHR25); indomethacin + 50 mg/kg chrysin (Indo + CHR50); indomethacin + 100 mg/kg chrysin (Indo + CHR100). All doses of chrysin were given orally to rats before indomethacin. Gastric lesions were examined macroscopically and microscopically. The effects of treatment with chrysin were assessed versus a single dose of 30 mg/kg Ulcuran® (generic ranitidine) as reference standard. We also investigated gastric mucosal superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), malonaldehyde (MDA) and arginase activities, and COX-2, PGE₂, iNOS, TNF-α, IL-1β, NFκB, MPO, Bax, caspase-3 and 8-OHdG levels. We assessed caspase-3 and Bax levels using immunohistochemistry. Compared to the control and reference groups, SOD, CAT, GPx and arginase activities and GSH levels decreased, and MDA levels increased in the indomethacin induced gastric ulcer group. iNOS, TNF-α, IL-1β, NFκB, MAPK-14, MPO, Bax and 8-OHdG levels were increased in the indomethacin treated gastric group, while COX-2 activity and PGE₂ levels were decreased. The three doses of chrysin co-administered with indomethacin increased COX-2 activity and PGE₂ levels in rats with ulcers. Chrysin exhibited gastroprotective effects on indomethacin induced gastric ulcer due to its antioxidant, anti-inflammatory and anti-apoptotic activities.