Atractylodin ameliorates lipopolysaccharide and D-galactosamine-induced acute liver failure via the suppression of inflammation and oxidative stress

Atractylodin (ACD) possesses versatile biological and pharmacological activities, including antibacterial, anti-inflammatory and hepatoprotective properties. However, the protective effects of ACD on lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced acute liver failure (ALF) as well as the underlying molecular mechanisms remain unclear. In this study, our findings showed that ACD treatment could reduce the high lethality rate; decrease the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), monocyte chemoattractant protein (MCP)-1, interleukin-1 beta (IL-1 beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha), and ameliorate the pathological hepatic damage of ALF. Furthermore, ACD pretreatment inhibited toll like receptor 4 (TLR4), nuclear factor kappa B (NF-kappa B), the mitogen-activated protein kinase (MAPK) and NOD-like receptor protein-3 (NLRP3) activation pathway. Moreover, our research showed that ACD could dramatically increase superoxide dismutase (SOD) and glutathione (GSH) production, and reduce COX-2, inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS) and malondialdehyde (MDA) production through upregulating the expression of the anti-oxidative enzymes heme oxygenase-1 (HO-1) and quinone (NQO1), which were related to the induction of nuclear transcription factor 2 (Nrf2) nuclear translocation. These results indicated that ACD exhibited anti-inflammatory activity, which was associated with the inhibition of inflammatory mediator production via the downregulation of the NLRP3 inflammasome and TLR4-NF-kappa B/-MAPK signaling pathways, and the antioxidative effects of ACD were connected with GSH and SOD activation through upregulation of the Nrf2-mediated signaling pathways.