title: Dioscin reduces lipopolysaccharide-induced inflammatory liver injury via regulating TLR4/MyD88 signal pathway.
abstract: We previously reported the effects of dioscin against carbon tetrachloride-, acetaminophen- and alcohol-induced acute liver damage. However, its effect on lipopolysaccharide (LPS)-induced inflammatory liver injury remains unknown. In the present work, liver injury in mice and rats was induced by LPS, and dioscin was intragastrically administered for 7days. In vitro, the AML-12 cells and HepG-2 cells were treated with LPS after dioscin treatment. The results showed that dioscin not only markedly reduced serum ALT, AST levels and relative liver weights, but also restored cell injury caused by LPS. In mechanism study, dioscin significantly attenuated inflammation through down-regulating the levels of toll-like receptor (TLR) 4, myeloid differentiation factor 88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylated inhibitor of nuclear factor κB kinase (p-IKK), phosphorylated inhibitor of nuclear factor κB alpha (p-IκBα), phosphorylated nuclear factor κB p65 (p-NF-κB p65), high-mobility group protein 1 (HMGB-1), interleukin (IL)-1, IL-6 and tumor necrosis factor-α (TNF-α). TLR4 overexpression was also decreased by dioscin, leading to the markedly decreased levels of MyD88, IRAK1, TRAF6, p-IKK, p-IκBα, p-NF-κB p65 and HMGB-1. Suppression of MyD88 by ST2825 eliminated the inhibitory effects of dioscin on the levels of IRAK1, TRAF6, p-IKK, p-IκBα, p-NF-κB p65, HMGB-1, IL-1β, IL-6 and TNF-α. Our results suggested that dioscin exhibited protective effect against LPS-induced liver injury via altering TLR4/MyD88 pathway, which should be developed as one potent candidate for the treatment of acute inflammatory liver injury in the future.
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Huanggang Polytechnic College, No. 109 Taoyuan St., Nanhu Educational District, Huanggang City 438002, Hubei Province, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Tao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China.
authors.forename: Changyuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Electronic address: jinyongpeng2008@126.com.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D016207:Cytokines / Q000378:metabolism; D027742:Dioscorea / Q000276:immunology*; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; C019357:dioscin; D004144:Diosgenin
keywords: Acute liver injury; Dioscin; Inflammation; Lipopolysaccharide; TLR4/MyD88 signal pathway