Isopulegol mitigates high glucose-induced oxidative stress in HK-2 cells via activation of the Nrf2/ARE pathway

Diabetic nephropathy (DN) represents a major contributor to chronic kidney disease, primarily resulting from oxidative stress and injury to renal tubules triggered by persistent hyperglycemia. This study evaluated the protective effects of isopulegol (IPG), a monoterpene on high glucose (HG)-induced cytotoxicity in HK-2 cell lines. Cytotoxicity assays (MTT and CCK-8) revealed the effect of IPG on cell viability in HK-2 cells under HG conditions, with an IC₅₀ of 45 µM. Treatment with IPG significantly improved the enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)] and glutathione (GSH) level, while reducing lipid peroxidation (LPO). Additionally, IPG promoted expression of Nrf2, activating the antioxidant response element (ARE) pathway. These findings suggest that IPG confers cytoprotective effects by enhancing antioxidant defense, reducing oxidative stress, highlighting its therapeutic potential in preventing oxidative renal damage in diabetic nephropathy.