Toxicological Mechanism of Triptolide-Induced Liver Injury

This study aimed to investigate the hepatotoxicity of triptolide (TRI) and its mechanism of action. The TRI-liver injury-pyroptosis association and the possible action targets were analyzed through network pharmacology, the molecular-protein docking analysis was conducted by the molecular docking method, and the binding mode between TRI and candidate targets was analyzed with dynamics simulation. In addition, the mouse model of TRI-induced liver injury was constructed in vitro to examine the influence of TRI on liver function. The expression levels of inflammatory factors were detected by ELISA, while pathological analysis was conducted by H&E staining and histochemical staining. As figured out from the network pharmacology analysis results, Caspase-3 might be the major action target of TRI, which was verified by molecular docking and dynamics simulation. Besides, the in vitro experimental results demonstrated that TRI induced liver injury in mice, enhanced the tissue inflammatory response. Caspase-3 may be the major target of TRI in liver injury, and TRI can mediate pyroptosis and tissue inflammatory response through Caspase-3 to induce acute liver injury.