title: Dioscin alleviates alcoholic liver fibrosis by attenuating hepatic stellate cell activation via the TLR4/MyD88/NF-κB signaling pathway.
abstract: The present work aimed to investigate the activities and underlying mechanisms of dioscin against alcoholic liver fibrosis (ALF). In vivo liver fibrosis in mice was induced by an alcoholic liquid diet, and in vitro studies were performed on activated HSC-T6 and LX2 cells treated with lipopolysaccharide. Our results showed that dioscin significantly attenuated hepatic stellate cells (HSCs) activation, improved collagen accumulation, and attenuated inflammation through down-regulating the levels of myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), interleukin (IL)-1, IL-6 and tumour necrosis factor-α by decreasing Toll-like receptor (TLR)4 expression both in vivo and in vitro. TLR4 overexpression was also decreased by dioscin, leading to the markedly down-regulated levels of MyD88, NF-κB, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) in cultured HSCs. Suppression of cellular MyD88 by ST2825 or abrogation of NF-κB by pyrrolidine dithiocarbamate eliminated the inhibitory effects of dioscin on the levels of TGF-β1, α-SMA and COL1A1. In a word, dioscin exhibited potent effects against ALF via altering TLR4/MyD88/NF-κB signaling pathway, which provided novel insights into the mechanisms of this compound as an antifibrogenic candidate for the treatment of ALF in the future.
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Dalian Medical University, No. 9 West Part of Lvshunnan Road, Dalian 116044, China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000818:Animals; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C019357:dioscin; D004144:Diosgenin