Combined Ursolic Acid and Rosuvastatin Treatment Mitigates Inflammation and Oxidative Stress in Diabetic Nephropathy Model Cells

BACKGROUND: Ursolic acid (UA) and Rosuvastatin (RST) improves diabetic nephropathy (DN). However, the combination therapy of UA and RST on DN and its possible mechanism requires exploration. METHODS: Streptozotocin (STZ)-induced DN model cells were treated with UA and RST alone or in combination. Cell viability and apoptosis were assessed using Cell Counting Kit-8 (CCK-8), flow cytometry, and TUNEL staining. The inflammation-related factors' release was examined by enzyme linked immunosorbent assay (ELISA). Potential mechanism was analyzed through network pharmacology. The reactive oxygen species (ROS) accumulation was detected using flow cytometry. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were measured using commercial reagent kits. RESULTS: UA and RST increased viability while reducing apoptosis of STZ-induced cells. UA and RST suppressed the release of inflammation-related factors in STZ-induced cells. Through network pharmacology analysis, the inflammation and oxidative stress were thought to be implicated in the treatment of UA and RST in DN. UA and RST downregulated ROS and MDA while upregulating SOD and CAT in STZ-induced cells. Compared with RST and UA used individually, their combination showed a more potent effect in increasing viability, mitigating apoptosis, and suppressing the inflammation and oxidative stress in STZ-induced cells. CONCLUSION: Combined UA and RST therapy ameliorated the inflammation and oxidative stress in DN model cells, providing the theoretical basis for pharmacological research of DN.