Abstract
• Exploring the regulatory effect of PD on CP-induced intestinal injury. • Demonstrating that PD exerts a certain protective effect on intestinal damage caused by CP. • Revealing that PD for alleviating CP-induced intestinal damage might be related to PERK-eIF2ɑ-ATF4 signaling pathway. The current study aimed to reveal the inhibitory effect of Platycodin D (PD) on intestinal cell apoptosis mediated by ER stress. Treatment with PD alleviated pathological changes of the intestine and reduced secretion of intracellular enzyme Diamine oxidase (DAO) in the upper villi of the small intestinal mucosa in Cisplatin (CP) intestinal injury model and increased expression of key protein Occludin and ZO-1 of the intestinal mechanical barrier. PD inhibited ER stress in a dose-dependent in CP-caused IEC-6 cells and the level of phosphorylation of Protein kinase R-like ERK kinase (PERK) and Eukaryotic initiation factor-2 alpha (eIF2α) reduced. Besides, the ER stress inhibitor 4-PBA was used to confirm that PD alleviated the ER stress in vitro . In conclusion, PD exerted an intestinal protective effect through the inhibition of ER stress in CP-treated mice and IEC-6 cells. These data indicated that PD was a promising natural medicine for intestinal protection.
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