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

Abstract

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.