Puerarin alleviates high glucose-induced lens epithelial cell damage by activating the Nrf2 Signaling pathway to inhibit oxidative stress.

Abstract

This study investigated Puerarin's protective effects and mechanisms against high glucose (HG)-induced damage in human lens epithelial cells (HLECs), which are relevant to diabetic complications. Using an HG-exposed HLEC model, varying doses of Puerarin (10 μM, 20 μM, 50 μM) were tested. While non-toxic to normal HLECs, both 20 μM and 50 μM Puerarin significantly and dose-dependently restored cell viability reduced by HG (P < 0.05). Puerarin effectively reversed HG-induced apoptosis and mitigated oxidative stress by increasing levels of antioxidant enzymes (SOD, GSH-Px) and decreasing malondialdehyde (MDA) concentrations. Mechanistically, Puerarin significantly upregulated the expression of the transcription factor Nrf2, with the strongest effect observed at 50 μM. Crucially, when Nrf2 expression was knocked down using shRNA Nrf2 transfection in HG-treated HLECs, the protective effects of high-dose Puerarin were completely abolished. This loss of protection resulted in significantly increased cell death and oxidative stress markers compared to control cells transfected with shRNA Ctrl and treated with Puerarin. The findings demonstrate that Puerarin, particularly at doses of 20 μM and 50 μM, protects HLECs from HG-induced damage in a dose-dependent manner. This protection involves preserving cell viability, reducing apoptosis, and enhancing cellular antioxidant defenses. The Nrf2 signaling pathway is identified as a key mechanism mediating Puerarin's beneficial effects. These results suggest that Puerarin has potential as a therapeutic agent for preventing diabetic complications affecting the lens epithelium.