Dioscin attenuates gastric ischemia/reperfusion injury through the down-regulation of PKC/ERK1/2 signaling via PKCα and PKCβ2 inhibition.

BACKGROUND: We previously reported the promising effects of dioscin against cerebral and renal ischemia-reperfusion (I/R) injury. However, its role against gastric I/R injury has not yet been reported. Thus, the aim of the present work was to investigate the protective effect and possible mechanisms of dioscin against gastric I/R.

MATERIALS AND METHODS: The hypoxia-reoxygenation (H/R) model in GES-1 cells and the celiac artery occlusion model in rats were carried out in the study.

RESULTS: Dioscin markedly attenuated H/R insult in GES-1 cells and gastric I/R injury in rats. Mechanistic studies demonstrated that dioscin-induced gastric protection was accompanied by inhibiting the levels of PKCα, PKCβ2 and phosphorylation via decreasing Raf-1 level. Blockade of PKC/ERK1/2 signaling pathway by dioscin decreased MEK1/2 level, ERK1/2 phosphorylation and the nuclear translocation, NF-κB and AP-1 transcriptional activities, pro-inflammatory cytokine responses, and up-regulated PPAR-γ level. Moreover, the results of small interfering RNA (siRNA) and overexpression of PKCα and PKCβ2 confirmed that dioscin attenuated gastric I/R injury through inhibiting PKC/ERK1/2 signaling by down-regulating PKCα and PKCβ2.

CONCLUSION: These data confirmed the protective effect of dioscin against gastric I/R injury, which should be developed as a therapeutic agent for the treatment of acute gastric mucosal lesions in the future.