Gentiopicroside ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling

摘要

Background: Excessive ethanol consumption results in gastric mucosa damage, which could further develop into chronic gastritis, peptic ulcer, and gastric cancer in humans. Gentiopicroside (GPS), a major active component of Gentianae Macrophyllae radix, was reported to play a critical role in anti-inflammation. In the study, we aimed to investigate the functional role and underlying mechanism of GPS in ethanol-induced gastritis. Methods: A model of gastritis was created by ethanol in C57BL/6 mice. Enzyme-linked immunosorbent assay was used to determine the concentration of TNF-alpha, IL-1 beta, IL-8, and IL-10. Results: We found that GPS treatment significantly ameliorated ethanol-induced gastritis in mice, with lower production of pro-inflammatory cytokine TNF-alpha, IL-1 beta, and IL-8 and higher levels of anti-inflammatory cytokine IL-10. The anti-inflammatory effect of GPS was further confirmed in vitro in ethanol-treated human gastric mucosal GES cells. Mechanistically, we demonstrated that GPS regulated matrix metallopeptidase expression and pERK1/2 signaling. Knockdown of matrix metallopeptidase 10 (MMP-10) greatly improved cell survival and suppressed inflammatory response in ethanol treated GES cells. Moreover, inhibition of pERK1/2 signaling using U0126 decreased the expression of MMP10 in ethanol-induced gastritis. U0126 treatment also suppressed the expression of TNF-alpha, IL-1 beta, and IL-8, and enhanced IL-10 expression in mice gastric mucosa. Conclusions: Taken together, our findings suggest that GPS ameliorates ethanol-induced gastritis via regulating MMP-10 and pERK1/2 signaling, which might provide a promising therapeutic drug for ethanol-induced gastritis.