Biphasic activity of resveratrol on indomethacin-induced gastric ulcers

Resveratrol showed biphasic activity in indomethacin-induced gastric ulcerated mice. A protective effect at a lower dose (2 mg kg−1) and a contraindicative effect at a higher dose of Resveratrol (10 mg kg−1) were observed. This phenomenon was possibly controlled by a COX-1 and eNOS balance, which ultimately maintained angiogenesis in Resveratrol-treated pre-ulcerated mice. The lower dose of Resveratrol (2 mg kg−1) augmented eNOS expression without altering COX-1 expression, but, at a higher dose (10 mg kg−1), Resveratrol predominantly suppressed COX-1 expression, which significantly reduced both PGE2 synthesis and angiogenesis. Thus it ultimately resulted in delay healing of indomethacin-induced gastric ulcers. Hence, it could be concluded that COX-1 and eNOS acted as key regulatory factors switching the biphasic effects of Resveratrol in indomethacin-induced ulcerated mice.