Targeted inhibition of STING-TBK1 axis alleviates the hepatotoxicity of tripterygium glycosides.

IntroductionThis study aimed to investigate the mechanisms underlying Tripterygium glycosides (TG) - induced liver injury, focusing on the role of the STING-TBK1 signaling pathway, and to evaluate the therapeutic potential of inhibiting this axis in mitigating liver damage.MethodsThe study employed two experimental approaches. First, male Balb/c mice were administered TG at doses of 13.5, 40.5, and 135 mg/kg for 3 weeks to assess dose-dependent hepatotoxicity. Liver injury was evaluated through serum ALT/AST levels, hepatic histopathology, and liver index. Immunohistochemical staining and Western blot analysis were used to examine STING expression in liver tissues and THP-1 cells. In the second approach, pharmacological inhibitors of STING and TBK1 were administered to evaluate their protective effects against TG-induced liver injury.ResultsTG induced dose-dependent liver injury and inflammatory infiltration, along with activation of the STING-TBK1 pathway in non-parenchymal cells. Inhibition of this pathway significantly attenuated hepatotoxicity, as evidenced by reduced ALT/AST levels, decreased inflammatory cytokines, and improved histopathological outcomes.DiscussionThese findings demonstrate that the STING-TBK1 axis plays a critical role in mediating TG-induced hepatotoxicity. Pharmacological inhibition of this pathway effectively alleviates TG-induced hepatotoxicity, suggesting its potential as a therapeutic target for drug-induced liver injury.