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 (CCl 4 )-induced acute liver injury was investigated. Celastrol improved the increased transaminase activity, inflammation, and oxidative stress induced by CCl 4 , 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 CCl 4 -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.