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

作者：Hu, Yupeng; Tao, Xufeng; Han, Xu; Xu, Lina; Yin, Lianhong; Qi, Yan; Zhao, Yanyan; Xu, Youwei; Wang, Changyuan; Peng, Jinyong^*

来源：Chemico-Biological Interactions, 2016, 258: 234-244.

DOI：10.1016/j.cbi.2016.09.014

• Anti-oxidative stress
• Dioscin
• Gastric ischemia-reperfusion
• Natural product
• PKC/ERK1/2 signaling pathway

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 PKC alpha, PKC beta 2 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-kappa B and AP-1 transcriptional activities, pro-inflammatory cytokine responses, and up-regulated PPAR-gamma level. Moreover, the results of small interfering RNA (siRNA) and overexpression of PKC alpha and PKC beta 2 confirmed that dioscin attenuated gastric I/R injury through inhibiting PKC/ERK1/2 signaling by downregulating PKC alpha and PKC beta 2.
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.

• 出版日期2016-10-25
• 单位大连医科大学