title: Anti-fibrotic effects of Astragaloside IV in systemic sclerosis.
abstract: OBJECTIVE
  To evaluate the anti-fibrotic effects of Astragaloside IV in systemic sclerosis.
  
  
  METHODS
  Treated or untreated systemic sclerosis (SSc) and normal fibroblast isolated from corresponding pairs were utilized to detect expression of collagen and fibronectin by western blot, quantitative real-time RT-PCR (RT-qPCR), immunofluorescence staining and histopathological examination. SSc mouse model induced by bleomycin was used to evaluate the effects of the drug in vivo.
  
  
  RESULTS
  Compared to normal fibroblast (NF), the expression of collagen and fibronectin in SSc (SScF) dramatically increased, and this could be reduced by Astragaloside IV (AST) in a dose- or time-dependent manner at both protein and mRNA levels. Administration of Astragaloside IV consistently decreased collagen formation and partially restored the structure, as well as suppressing collagen and fibronectin expression in the skin lesions of SSc-model mice. Mechanistically, Astragaloside IV-induced fibrosis reduction may be due to deregulation of Smad 3/Fli-1, the major mediators of the fibrotic response and key molecules for TGF-β signaling. Astragaloside IV also decreased the level of p-SMAD3 and completely blocked its relocation into the nuclei.
  
  
  CONCLUSIONS
  Astragaloside IV attenuates fibrosis by inhibiting the TGF-β-Smads3 axis in systemic sclerosis.
authors.affiliation: Department of Dermatology, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Qi
authors.forename: Yueping
authors.initials: Y
authors.lastname: Mao
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Yi
authors.forename: Donghai
authors.initials: D
authors.lastname: Li
authors.forename: Ke
authors.initials: K
authors.lastname: Zhu
authors.forename: Xushan
authors.initials: X
authors.lastname: Cha
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005347:Fibroblasts; D005355:Fibrosis / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D051379:Mice; D012333:RNA, Messenger; D012503:Saponins / Q000008:administration & dosage*; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D051900:Smad3 Protein / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014315:Triterpenes / Q000008:administration & dosage*
chemical_list: D012333:RNA, Messenger; D012503:Saponins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D016212:Transforming Growth Factor beta; D014315:Triterpenes; C052064:astragaloside A