Protective and therapeutic effects of the flavonoid pinocembrin in indomethacin-induced acute gastric ulcer in rats: impact of anti-oxidant, anti-inflammatory, and anti-apoptotic mechanisms

Peptic ulcer including gastric and duodenal ulcers is a common gastro-intestinal disorder worldwide, associated with a significant mortality due to bleeding and perforation. Numerous efforts are being exerted to look for natural drugs that lack the potential side effects but still keep beneficial effects for treatment and/or prevention of gastric ulcer. Pinocembrin (PINO) is a natural flavonoid retaining anti-microbial, anti-oxidant, and anti-inflammatory activities. The present study was conducted to investigate the protective and therapeutic effects of PINO against indomethacin (INDO)-induced gastric ulcer in rats and the possible underlying mechanisms. PINO (25 and 50 mg/kg) promoted mucus secretion, decreased ulcer index, and inhibited histopathological changes induced by INDO. Further investigation of possible mechanisms showed that PINO significantly attenuated INDO-induced oxidative and inflammatory responses in both doses when administrated before or after ulcer induction. PINO downregulated mRNA expression level of p38-mitogen-activated protein kinase (p38-MAPK) which subsequently inhibited NF-kappa B activation and inflammatory cytokine release including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta). Additionally, PINO inhibited apoptotic activity which was confirmed by downregulation of caspase-3 transcription. The current results demonstrated the promising therapeutic activity of PINO against INDO-induced gastric ulcer due to-at least partly-its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.

Automated summary

The study investigated the protective and therapeutic effects of pinocembrin (PINO) against indomethacin (INDO)-induced gastric ulcer in rats. Results showed that PINO promoted mucus secretion, decreased ulcer index, and inhibited histopathological changes induced by INDO. PINO also attenuated INDO-induced oxidative and inflammatory responses by downregulating mRNA expression level of p38-MAPK and inhibiting NF-kappa B activation. Additionally, PINO inhibited apoptotic activity by downregulating caspase-3 transcription. These findings suggest that PINO has promising therapeutic activity against INDO-induced gastric ulcer due to its anti-oxidant, anti-inflammatory, and anti-apoptotic effects.