Protective effect of cornel iridoid glycoside against isoniazid- and rifampicin- induced liver injury via regulating JAK/STAT pathway.

BACKGROUND

Hepatotoxicity associated with Isoniazid (INH) and Rifampicin (RIF) is one of the major impediments in antituberculosis therapy.

PURPOSE: We aimed to investigate the protective effects of the cornel iridoid glycoside (CIG) on liver injury caused by INH and RIF in vivo and in vitro.

METHODS

Liver injury model was induced by INH and RIF (150 mg/kg). Then the mice were orally administered with CIG (50, 100, and 200 mg/kg) and silymarin (100 mg/kg) for 2 weeks. HepG2 cells were treated with 0.1 mg/ml INH and 0.2 mg/ml RIF to establish injury model. Blood samples and cell lysis were used for biochemical analysis and western blot assay. Liver tissues were harvested for histological examination.

RESULTS

Treatment of CIG significantly restored liver function, reduced the levels of inflammatory factors, enhanced the antioxidant activity, and alleviated lipid metabolism disorder compared with the model group in vivo. CIG restored cell viability and activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) in vitro. Furthermore, CIG inhibited the protein expression of JAK/STAT pathway.

CONCLUSIONS

CIG is effective in preventing INH and RIF-induced hepatotoxicity in vivo and in vitro. These findings provide scientific basis for the clinical application of cornel in treating liver injury.