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

Abstract：

: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-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), and ameliorate the pathological hepatic damage of ALF. Furthermore, ACD pretreatment inhibited toll like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), 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-κB/-MAPK signaling pathways, and the antioxidative effects of ACD were connected with GSH and SOD activation through upregulation of the Nrf2-mediated signaling pathways.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Lyu Z,Ji X,Chen G,An B

doi

10.1016/j.intimp.2019.04.005

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

348-357

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)30002-5

journal_volume

pub_type

杂志文章

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