Panax Notoginseng Saponins Alleviate High Glucose-Induced Glomerular Endothelial Cell Injury by Inhibiting the ET-1/PKC/TGF-β1 Signaling Pathway

Abstract

This study aimed to investigate the protective effects and underlying mechanisms of Panax notoginseng saponins (PNS) on glomerular endothelial cell (GEC) injury induced by high glucose, which is crucial in the development of diabetic nephropathy. GECs were treated with high glucose alone, PNS alone, or a combination of PNS and overexpression of endothelin-1 (ET-1), a key regulator in endothelial dysfunction. The results showed that high glucose inhibited cell viability, increased reactive oxygen species (ROS) levels, and upregulated the expression of fibronectin (FN), collagen type IV (Col-IV), protein kinase C (PKC), transforming growth factor-beta 1 (TGF-β1), and ET-1. Additionally, high glucose downregulated the expression of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). PNS treatment significantly protected against high glucose-induced GEC injury by promoting cell viability, reducing ROS generation, downregulating FN, Col-IV, PKC, TGF-β1, and ET-1 expression, and upregulating SOD, GSH-Px, and CAT expression. However, ET-1 overexpression reversed the protective effects of PNS, indicating the involvement of the ET-1/protein kinase C (PKC)/TGF-β1 pathway. In conclusion, PNS demonstrated a protective effect against high glucose-induced GEC injury by inhibiting the ET-1/PKC/TGF-β1 pathway. These findings suggest that PNS may be a potential therapeutic target for diabetic nephropathy by antagonizing ET-1.