Polygonatum sibiricum polysaccharides ameliorate diabetes-induced vascular endothelial injury partly through Nrf2/GPX4 activation.

Diabetes mellitus is a chronic metabolic disorder in which endothelial dysfunction plays a pivotal role in disease progression. Polygonatum sibiricum polysaccharides (PSP) exhibit multiple biological activities, including antioxidant effects, anti-apoptotic action, and regulation of lipid metabolism. However, the mechanisms by which PSP protects against diabetic endothelial injury remain poorly understood. Therefore, this study aimed to elucidate the protective role and underlying mechanisms of PSP in diabetes-induced vascular endothelial injury. In this study, PSP treatment markedly alleviated diabetes-induced vascular endothelial injury, reduced serum TG and LDL levels in streptozotocin (STZ)-induced diabetic rats. Proteomic enrichment analysis revealed that PSP modulates multiple molecular pathways related to oxidative stress, lipid metabolism, and apoptosis. Further experiments showed that PSP treatment restored mitochondrial membrane potential, enhanced cell viability, suppressed Caspase-3 and Bax expression, and upregulated Bcl-2 to attenuate palmitic acid (PA)-induced apoptosis in endothelial cells. Moreover, PSP reduced lipid peroxidation products (ROS and MDA) and upregulated the expression of Nrf2 and GPX4. In conclusion, PSP effectively alleviates diabetes-induced vascular endothelial injury by improving lipid metabolism, inhibiting apoptosis and oxidative stress, partly through activation of the Nrf2/GPX4 pathway. These findings highlight the potential of PSP as a therapeutic agent for diabetes.