Abstract:

AIM: To investigate the role and mechanism of triptolide (TP) in mediating liver cell damage through activation of the JNK pathway. METHODS: Using human hepatocellular carcinoma cells HepG2 and primary mouse hepatocytes, exposure to different doses (25, 50, 100 nmol/L) and times was conducted to assess liver cell viability and function by measuring ALT and AST levels; Western blotting was employed to detect the expression levels of JNK pathway-related proteins; the JC-1 fluorescent probe was used to detect changes in mitochondrial membrane potential; the specific JNK inhibitor SP600125 (SP) was used for intervention verification. RESULTS: After exposure to different doses of TP for 24 hours, the levels of ALT and AST in the culture medium significantly increased (P<0.05), simultaneously dose-dependently inhibiting HepG2 cell viability; Western blotting detected that p-JNK expression in HepG2 cells and mouse primary liver cells under different doses and times of TP treatment showed a positive correlation with TP concentration and exposure time; the JC-1 assay revealed significant changes in mitochondrial membrane potential in HepG2 cells treated with different doses of triptolide for 24 hours, leading to mitochondrial damage and inhibition of liver cell viability, with the degree of damage correlating positively with dose; pre-exposure to the JNK inhibitor SP significantly reversed the TP-induced activation of p-JNK, resulting in significantly lower ALT and AST levels compared to the TP group (P<0.05), restoring cell viability. CONCLUSION: TP can significantly inhibit liver cell viability and impair their function, possibly by activating the JNK pathway and causing mitochondrial damage.

Key words: triptolide, liver toxicity, JNK pathway, liver damage