title: Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated NAD(P)H oxidase activation and Smad signaling in vivo and in vitro.
abstract: OBJECTIVE
  We studied that a potent antifibrotic effect of decursin on in vivo liver damage model and the mechanism in inhibiting which transforming growth factor (TGF)-β1-induced human hepatic stellate cells (HSCs) activation.
  
  
  METHODS
  Liver injury was induced in vivo by intraperitoneal injection of carbon tetrachloride (CCl4) with or without decursin for 4weeks in mice. Human hepatic stellate cell line, an immortalized human HSC line, was used in in vitro assay system. The effects of decursin on HSC activation were measured by analyzing the expression of α-smooth muscle actin (α-SMA) and collagen I in liver tissue and human HSCs.
  
  
  RESULTS
  Decursin treatment significantly reduced the ratio of liver/body weight, α-SMA activation, and type I collagen overexpression in CCl4 treated mice liver. The elevated serum levels, including ALT, AST, and ALP, were also decreased by decursin treatment. Treatment of decursin markedly proved the generation of reactive oxygen species, NAD(P)H oxidase (NOX) protein (1, 2, and 4) upregulation, NOX activity, and superoxide anion production in HSCs by TGF-β1. It also significantly reduced TGF-β1-induced Smad 2/3 phosphorylation, nuclear translocation of Smad 4, and association of Smad 2/3-Smad 4 complex. Consistent with in vitro results, decursin treatment effectively blocked the levels of NOX protein, and Smad 2/3 phosphorylation in injured mice liver.
  
  
  CONCLUSIONS
  Decursin blocked CCl4-induced liver fibrosis and inhibited TGF-β1-mediated HSC activation in vitro. These data demonstrated that decursin exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling.
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Young Ji
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Da Hye
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Ju
authors.initials: J
authors.lastname: Kim
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Seung-Il
authors.initials: SI
authors.lastname: Jeong
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Chung
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea. Electronic address: Kangyu@jbmi.re.kr.
authors.forename: Kang-Yeol
authors.initials: KY
authors.lastname: Yu
authors.affiliation: Jeonju Biomaterials Institute, Jeonju, Chonbuk, Republic of Korea. Electronic address: Seon02@jbmi.re.kr.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D001578:Benzopyrans; D002087:Butyrates; D024042:Collagen Type I; D017382:Reactive Oxygen Species; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D002251:Carbon Tetrachloride; C101278:decursin; D019255:NADPH Oxidases
keywords: Decursin; Liver fibrosis; NADPH oxidase; ROS; TGF-beta