Antioxidation, anti-inflammation and anti-apoptosis by paeonol in LPS/D-GalN-induced acute liver failure in mice

To evaluate the hepatoprotective effects and potential mechanisms of paeonol (Pae) against acute liver failure (ALF) induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN) in mice, we examined anti-oxidative, anti-inflammatory and anti-apoptotic activities of Pae. We found that Pae pretreatment markedly reduced the activities of alanine transaminase and aspartate transaminase as well as the histopathological changes induced by LPS/o-GalN. Catalase, glutathione and superoxide dismutase activities increased and reactive oxygen species activity decreased after Pae treatment compared with LPS/D-GalN treatment. Pretreatment with Pae also significantly inhibited the expression levels of iNOS, nitric oxide (NO), COX-2 and prostaglandin E-2 (PGE(2)). In addition, Pae administration prevented the phosphorylated expression of I kappa B kinase, inhibitor kappa B in the nuclear factor-kappa B (NF-kappa B) signaling pathway, and suppressed the phosphorylated expression of extracellular signal-regulated kinase (ERK), c-jun-N-terminal kinase and p38 in the MAPK signaling pathway. Pretreatment with Pae also inhibited hepatocyte apoptosis by reducing the expression of caspases 3, 8, 9, and Bax, and increasing Bcl-2. In total, protective effects of Pae against LPS/D-GalN-induced ALF in mice are attributed to its antioxidative effect, inflammatory suppression in NF-kappa B and MARK signaling pathways, and inhibition of hepatocyte apoptosis inhibition. Therefore, Pae can be a potential therapeutic agent in attenuating LPS/D-GalN-induced ALF in the future. (C) 2017 Published by Elsevier B.V.