Mechanisms underlying gastroprotective effect of paeonol against indomethacin-induced ulcer in rats

Paeonol, a natural phenolic compound, possesses diverse beneficial effects including antioxidant and anti-inflammatory effects. Gastric ulcer is still the most prevalent irritant illness among the gastrointestinal diseases. The present study explored the protective effect of paeonol at two dose levels in indomethacin (IND)-induced gastric ulcer in rats. Forty-eight male Wistar rats were arranged into six groups: control, paeonol-treated, IND-treated, IND/paeonol (low and high doses)-treated, and ranitidine-treated groups. The oxidative status was evaluated by determining malondialdehyde level, superoxide dismutase activity, reduced glutathione content as well as hemoxygenase-1 (HO-1) gene expressions, and the antioxidant protein; NAD(P)H quinone oxidoreductase 1 (NQO1) immunostaining. The pro-inflammatory genes nuclear factor κB (NF-κB) and interleukin 1β (IL-1β) were estimated together with the proapoptotic gene of caspase 3. IND caused multiple gastric ulcers with evident oxidative damage and elevated pro-inflammatory and proapoptotic markers. Paeonol protected significantly, in a dose-dependent manner, the gastric mucosa from ulcerative lesion of IND similar to the reference drug ranitidine. Paeonol pretreatment diminished gastric oxidative stress and restored the gastric antioxidant capacity by elevating gastric gene expression of HO-1 and protein expression of NQO1. Paeonol also reduced NF-κB, IL-1β, and caspase 3 gene expressions. In conclusion, paeonol offered a gastroprotection dependent on its antioxidant, anti-inflammatory, and antiapoptotic effects.