<i>Moringa oleifera</i> Leaf Extract Enhances the Viability and Inhibits Ferroptosis in High Glucose-induced Rat Podocytes by Downregulating ACSL4

Background Diabetic nephropathy (DN) is a severe complication in patients with diabetes mellitus, which is mainly characterized by glomerular podocyte injury. Ferroptosis is crucial in the pathogenesis of DN. Moringa oleifera leaf extract (MOLE) has attracted attention due to its multiple pharmacological activities, but it is unclear whether it can delay the progression of DN by inhibiting ferroptosis. Objectives To investigate whether MOLE can alleviate podocyte injury and delay the progression of DN by inhibiting ferroptosis. Materials and Methods DN model cells were established using rat podocytes induced by high glucose (HG); the cells were processed with MOLE, dapagliflozin (DAPA, positive control), and acyl-CoA synthetase long-chain family member 4 (ACSL4) overexpression plasmids. Cell viability, Fe 2+ concentration, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) levels were monitored by Cell Counting Kit-8 (CCK-8) and corresponding kits. Results MOLE treatment markedly enhanced HG-induced rat podocyte viability, decreased intracellular Fe 2+ concentration, ROS level, MDA concentration, and elevated GSH concentration. ACSL4 overexpression reversed the protective effect of MOLE on podocytes. Conclusion MOLE ameliorates rat podocyte injury and delays DN progression by inhibiting ACSL4-mediated ferroptosis. This finding provides a theoretical basis for further developing MOLE-based therapeutic agents for DN treatment.