title: Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway.
abstract: Hepatic stellate cells (HSCs) are key mediators of fibrogenesis, and the regulation of their activation is now viewed as an attractive target for the treatment of liver fibrosis. Here, the authors investigated the ability of sauchinone, an active lignan found in Saururus chinensis, to regulate the activation of HSCs, to prevent liver fibrosis, and to inhibit oxidative stress in vivo and in vitro. Blood biochemistry and histopathology were assessed in CCl4-induced mouse model of liver fibrosis to investigate the effects of sauchinone. In addition, transforming growth factor-β1 (TGF-β1)-activated LX-2 cells (a human HSC line) were used to investigate the in vitro effects of sauchinone. Sauchinone significantly inhibited liver fibrosis, as indicated by decreases in regions of hepatic degeneration, inflammatory cell infiltration, and the intensity of α-smooth muscle actin staining in mice. Sauchinone blocked the TGF-β1-induced phosphorylation of Smad 2/3 and the transcript levels of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 as well as autophagy in HSCs. Furthermore, sauchinone inhibited oxidative stress, as assessed by stainings of 4-hydroxynonenal and nitrotyrosine: these events may have a role in its inhibitory effects on HSCs activation. Sauchinone attenuated CCl4-induced liver fibrosis and TGF-β1-induced HSCs activation, which might be, at least in part, mediated by suppressing autophagy and oxidative stress in HSCs.
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Hye Lim
authors.initials: HL
authors.lastname: Seo
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Sae Kwang
authors.initials: SK
authors.lastname: Ku
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Jong Rok
authors.initials: JR
authors.lastname: Lee
authors.affiliation: College of Oriental Medicine, Dongeui University, Busan 614-851, Republic of Korea.
authors.forename: Soon Shik
authors.initials: SS
authors.lastname: Shin
authors.affiliation: College of Oriental Medicine, Dongguk University, Gyeongju, Gyeongbuk 780-714, Republic of Korea.
authors.forename: Sun-Dong
authors.initials: SD
authors.lastname: Park
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea.
authors.forename: Sang Chan
authors.initials: SC
authors.lastname: Kim
authors.affiliation: College of Oriental Medicine, Daegu Haany University, Daegu 706-828, Republic of Korea. Electronic address: ywkim@dhu.ac.kr.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology*; D002251:Carbon Tetrachloride; D002460:Cell Line; D004149:Dioxoles / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D032134:Saururaceae; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D000447:Aldehydes; D001578:Benzopyrans; D004149:Dioxoles; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020011:Protective Agents; D017382:Reactive Oxygen Species; C497782:SMAD2 protein, human; C497790:SMAD3 protein, human; D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; C410958:sauchinone; D002251:Carbon Tetrachloride; C027576:4-hydroxy-2-nonenal
keywords: Carbon tetrachloride; Hepatic stellate cells; Liver fibrosis; Sauchinone; TGF-β1