LAUSR

Abstract 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/d‐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 E2 (PGE2). In addition, Pae administration prevented the phosphorylated expression of I&kgr;B kinase, inhibitor kappa B in the nuclear factor‐kappa B (NF‐&kgr;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‐&kgr;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. Graphical abstract Figure. No Caption available. HighlightsProtecting mechanism of Pae on LPS/d‐GalN‐induced ALF in mice was systematically evaluated.Pae exhibited great anti‐oxidative stress, anti‐inflammation and anti‐apoptosis activities.The liver protective effects of Pae are through NF‐&kgr;B and MAPK signal pathway.