AIM Cryptotanshinone (CTN), one of the major constituents of tanshinones, was investigated for hepatoprotective effects in D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure mouse model.METHODS CTN (20 or 40 mg·kg-1) was orally administered 12 and 1 h prior to D-GaiN (700 mg·kg-1)/LPS (10 μg·kg-1) injection.RESULTS Pretreatment with CTN markedly protected mice from lethal liver injury, which has known to be associated with a massive hepatocyte apoptosis.Indeed, CTN significantly blocked the elevation of TNF-αt and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well.CTN also remarkably reduced DNA fragmentation in the liver, which correlated with blockade of caspase 3,caspase 8, and caspase 9 activation.Moreover, increased cytosolic cytochrome c protein was reduced by CTN.In addition, CTN significantly suppressed the activation of JNK, ERK and p38 induced by D-GalN/LPS, and phosphorylation of TAK1 as well.Furthermore, CTN significantly inhibited the activation of nuclear factor (NF)-κB and suppressed production of inflammatory mediators.CONCLUSION These findings suggested that CTN prevents D-GaiN/LPS-induced fulminant hepatic failure, and this protection is likely associated with its anti-apoptotic activity and the down-regulation of MAPK activity associated at least in part with suppressing NF-κB.