Integration of network pharmacology and transcriptomics to reveal the ROS/NLRP3/Caspase-1/GSDMD-mediated mechanism of baicalin in alleviating contrast-induced acute kidney injury

Contrast-induced acute kidney injury (CI-AKI) is a major hospital-acquired renal dysfunction for which therapeutic options are limited. Scutellariae radix has traditional anti-inflammatory effects, and its main component baicalin shows potent anti-inflammatory/antioxidant activities. However, baicalin's in vivo efficacy and mechanisms in CI-AKI remain unclear. This study aimed to evaluate its therapeutic effect on iohexol-induced CI-AKI and elucidate the underlying mechanisms. C57BL/6 mice were assigned to control, CI-AKI model, and baicalin-pretreated (50 mg/kg and 100 mg/kg) groups. After CI-AKI induction, serum Scr and BUN, renal histopathology (H&E/PAS staining, RTI scores), oxidative stress (SOD, GSH-Px, MDA), and inflammation (IL-1β and IL-18) were assessed. Network pharmacology (NP) predicted baicalin's targets/pathways, and transcriptomic Sequencing identified differentially expressed genes (DEGs) in the kidne. Inhibitor experiments validated the key pathway. Baicalin reduced Scr/BUN levels, alleviated renal tubular vacuolar degeneration, lowered RTI scores, regulated oxidative stress markers, and downregulated IL-1β and IL-18. NP identified 129 overlapping targets enriched in inflammation pathways; transcriptomics found 308 key DEGs. Integrated analysis highlighted the ROS/NLRP3/Caspase-1/GSDMD pathway, with baicalin's downregulation of the NLRP3/Caspase-1/GSDMD confirmed by inhibitors. Baicalin alleviates iohexol-induced CI-AKI by inhibiting the ROS/NLRP3/Caspase-1/GSDMD pathway, providing a basis for clinical application.