Coptisine Protects Against Cisplatin‐Induced Acute Kidney Injury With Involvement of PI3K/Akt Signaling

Cisplatin is an effective chemotherapeutic agent whose clinical use is limited by nephrotoxicity. This study investigated the protective effects of coptisine, a bioactive alkaloid from Coptis chinensis , against cisplatin‐induced acute kidney injury (AKI). Network pharmacology was used to predict potential targets and pathways. Cisplatin‐treated HK‐2 cells and lipopolysaccharide‐stimulated RAW264.7 macrophages were used to evaluate oxidative stress, apoptosis, and inflammation. LY294002 was used to assess the functional contribution of phosphatidylinositol 3‐kinase/protein kinase B (PI3K/Akt) signaling. A cisplatin‐induced AKI mouse model was used to evaluate renal injury, oxidative stress, and early profibrotic remodeling. Network pharmacology identified PI3K/Akt as a potential pathway associated with coptisine. In HK‐2 cells, coptisine improved cell viability, reduced reactive oxygen species accumulation, lipid peroxidation, and apoptosis, and restored antioxidant defenses. In RAW264.7 macrophages, coptisine reduced pro‐inflammatory cytokine production and inducible nitric oxide synthase and cyclooxygenase‐2 expression. In mice, coptisine decreased serum blood urea nitrogen and creatinine levels, reduced renal levels of kidney injury molecule‐1 and neutrophil gelatinase‐associated lipocalin, and attenuated tubular injury, collagen deposition, and α‐smooth muscle actin expression. Cisplatin reduced the p‐PI3K/PI3K and p‐Akt/Akt ratios in HK‐2 cells and kidney tissues, whereas coptisine restored both ratios. LY294002 partially attenuated the cytoprotective, antioxidant, and anti‐apoptotic effects of coptisine in HK‐2 cells. Collectively, coptisine alleviates cisplatin‐induced AKI by suppressing oxidative stress, apoptosis, and inflammation, with PI3K/Akt signaling contributing to its cytoprotective effects.