Celastrol ameliorates acute liver injury through modulation of PPARα

Celastrol, derived from the roots of the Tripterygium Wilfordi, has attracted interest for its potential anti-inflammatory and lipid-lowering activities. In the present study, the protective effect of celastrol on carbon tetrachloride (CCl4)-induced acute liver injury was investigated. Celastrol improved the increased transaminase activity, inflammation, and oxidative stress induced by CCl4, resulting in improved metabolic disorders found in mice with liver injury. Dual-luciferase reporter assays and primary hepatocyte studies demonstrated that the peroxisome proliferator-activated receptor α (PPARα) signaling mediated the protective effect of celastrol, which was not observed in Ppara-null mice, and co-treatment of wild-type mice with the PPARα antagonist GW6471. Mechanistically, PPARα deficiency potentiated CCl4-induced liver injury through a deoxycholic acid (DCA)-EGR1-inflammatory factor axis. These data demonstrate a novel role for celastrol in protection against acute liver injury through modulating PPARα signaling.