Dihydrotanshinone I attenuates cisplatin‐induced acute kidney injury by targeting TRIM28‐mediated oxidative stress and apoptosis: insights from activity‐based protein profiling and omics integration

Abstract Cisplatin, a platinum‐based chemotherapeutic agent, is widely used in cancer treatment, but its limitation lies in its nephrotoxicity, which compromises its clinical use. This study investigated the therapeutic potential of dihydrotanshinone I (DHT), a natural diterpene from Salvia miltiorrhiza , in mitigating cisplatin‐induced nephrotoxicity via dual antioxidant and antiapoptotic mechanisms. Using activity‐based protein profiling, we identified tripartite motif containing 28 (TRIM28) as a direct molecular target of DHT in human proximal tubule epithelial cells. DHT treatment significantly attenuated cisplatin‐induced cytotoxicity through TRIM28‐mediated reduction of reactive oxygen species (ROS) accumulation and inhibition of apoptotic signaling. Proteomic analysis revealed that DHT restored cisplatin‐altered protein expression linked to oxidative stress and apoptosis pathways. Pretreatment with DHT (15 mg kg −1 day −1 , oral gavage) in cisplatin‐treated C57BL/6 mice preserved the renal function, reduced the acute tubular injury, and reversed the cisplatin‐induced oxidative imbalance (enhanced superoxide dismutase activity, reduced malondialdehyde and ROS) and apoptotic signaling (BAX/Bcl‐2, c‐caspase 3) via in vivo experiments. These findings suggest that DHT is a promising renoprotective adjuvant for platinum‐based chemotherapy.