title: Emodin ameliorated lipopolysaccharide-induced fulminant hepatic failure by blockade of TLR4/MD2 complex expression in D-galactosamine-sensitized mice.
abstract: Emodin has been reported to possess anti-inflammatory and anti-oxidant activities. The aim of this study was to explore the effect and mechanism of emodin on lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in D-galactosamine (D-GalN)-sensitized mice. Our results showed that pretreatment with emodin inhibited the elevation of plasma aminotransferases, alleviated the hepatic histopathological abnormalities and improved the survival rate of LPS/D-GalN-primed mice. Moreover, emodin markedly attenuated the increased serum and hepatic tumor necrosis factor-α (TNF-α) production, and activated hepatic p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signal pathways in LPS/D-GalN-challenged mice. Furthermore, using an in vitro experiment, we found that emodin dose-dependently suppressed TNF-α production, dampened AP-1 and NF-κB activation, and blocked toll-like receptor (TLR) 4/myeloid differentiation factor (MD) 2 complex expression in LPS-elicited RAW264.7 mouse macrophage cells. Taken together, these data suggested that emodin could effectively prevent LPS-induced FHF, which might be mediated by inhibition of TNF-α production, deactivation of MAPKs and NF-κB, and blockade of TLR4/MD2 complex expression.
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Anatamy, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.affiliation: Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Kuang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Xu
authors.affiliation: Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China. Electronic address: jywan@cqmu.edu.cn.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002478:Cells, Cultured; D004642:Emodin / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005688:Galactosamine / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D008070:Lipopolysaccharides / Q000378:metabolism; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000188:drug therapy*; D051218:Lymphocyte Antigen 96 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008070:Lipopolysaccharides; C411728:Ly96 protein, mouse; D051218:Lymphocyte Antigen 96; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D048049:Extracellular Signal-Regulated MAP Kinases; D004642:Emodin
keywords: Emodin; Fulminant hepatic failure; Lipopolysaccharide; TNF-α; Toll-like receptor 4