Hepatoprotective effect of cryptotanshinone from Salvia miltiorrhiza in D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure

Abstract

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.

Keywords: ALT; AST; Apoptosis; Cryptotanshinone; ERK; FHF; Fulminant hepatic failure; GAPDH; GalN; IL-1; JNK; LPS; MAPK; NF-κB; Salvia miltiorrhiza; TAK1; TGF-β-activated kinase 1; TNF-α; alanine aminotransferase; aspartate aminotransferase; c-Jun N-terminal kinase; d-galactosamine; extracellular signal regulated kinase; fulminant hepatic failure; glyceraldehydes-3-phosphate dehydrogenase; interleukin-1; lipopolysaccharide; mitogen-activated protein kinases; nuclear factor-κB; tumor necrosis factor-α.