Oleanolic acid ameliorates podocyte injury by increasing autophagy to attenuate diabetic nephropathy

ObjectivesConventional pharmacotherapies afford only modest renoprotection in diabetic nephropathy (DN). Oleanolic acid (OA), a pentacyclic triterpenoid abundant in Traditional Chinese Medicine (TCM), mitigates DN, but its mechanism remains unclear. This study aimed to verify the hypothesis that OA protects podocytes by modulating autophagy, thereby exploring the potential therapeutic mechanism of OA in attenuating DN.MethodsHigh glucose-injured MPC5 podocytes were treated with OA to evaluate its impact on autophagy. Podocytes were further treated with graded concentrations of OA, rapamycin (an autophagy inducer), or 3-methyladenine (an autophagy inhibitor). Cell viability was quantified using the Cell Counting Kit-8 assay. Nuclear morphology was visualized by DAPI staining, autophagosomes were enumerated by transmission electron microscopy, and the expression of autophagy-related genes was determined by quantitative reverse transcription polymerase chain reaction. These complementary approaches were used to assess high-glucose-induced podocyte injury and the capacity of OA to enhance autophagy and attenuate cellular damage.Key findingsThe effective concentration window for OA was established at 5–10 μM. Within this concentration range, podocyte viability was significantly increased, accompanied by a higher autophagosome count and elevated expression of autophagosomal markers.ConclusionsOleanolic acid alleviates high glucose-induced podocyte injury by robustly activating autophagy, underscoring its potential as a sustainable therapeutic strategy for DN, along with other active compounds derived from TCM.