phenanthrenes and Liver-Failure--Acute

Cryptotanshinone from Salvia miltiorrhiza Bunge was investigated for hepatoprotective effects in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Cryptotanshinone (20 or 40 mg/kg) was orally administered 12 and 1h prior to GalN (700 mg/kg)/LPS (10 μg/kg) injection. The increased mortality and TNF-α levels by GalN/LPS were declined by cryptotanshinone pretreatment. In addition, cryptotanshinone attenuated GalN/LPS-induced apoptosis, characterized by the blockade of caspase-3, -8, and -9 activation, as well as the release of cytochrome c from the mitochondria. In addition, cryptotanshinone significantly suppressed JNK, ERK and p38 phosphorylation induced by GalN/LPS, and phosphorylation of TAK1 as well. Furthermore, cryptotanshinone significantly inhibited the activation of NF-κB and suppressed the production of proinflammatory cytokines. These findings suggested that hepatoprotective effect of cryptotanshinone is likely associated with its anti-apoptotic activity and the down-regulation of MAPKs and NF-κB associated at least in part with suppressing TAK1 phosphorylation.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Aspartate Aminotransferases; Caspases; Chemical and Drug Induced Liver Injury; Cytochromes c; Galactosamine; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; MAP Kinase Kinase Kinases; Mice; Mice, Inbred C57BL; Mitochondria; Mitogen-Activated Protein Kinases; NF-kappa B; Phenanthrenes; Phytotherapy; Plant Extracts; Salvia miltiorrhiza; Tumor Necrosis Factor-alpha