title: Hydrolysable tannins of tropical almond show antifibrotic effects in TGF-β1-induced hepatic stellate cells.
abstract: BACKGROUND
  Persistent activation of hepatic stellate cells (HSC-T6) has been known to cause liver fibrosis. In this study, our objective was to investigate the effects of chebulagic acid and chebulinic acid, two hydrolysable tannins of tropical almond (Terminalia chebula) fruits, on collagen synthesis and signal transduction in transforming growth factor-β1-stimulated HSC-T6 cells. The expression of Smad2, Smad3, Smad4, collagen I(α1)/III, and plasminogen activator inhibitor 1 (PAI-1) mRNAs was determined by reverse-transcription polymerase chain reaction and their protein levels were assessed by western blotting.
  
  
  RESULTS
  Results showed that chebulagic acid and chebulinic acid at 20 µmol L(-1) exhibited cytotoxic and anti-proliferative effects on HSC-T6 cells. They also significantly decreased the expression of Smd2, Smad3 and Smad4, and the synthesis of collagen, procollagen I (α1) and III, as well as suppressing the activation of PAI-1; these events consequently facilitated the resolution of fibrosis.
  
  
  CONCLUSIONS
  These results indicate that both chebulagic acid and chebulinic acid possess antifibrotic activity, and their mechanism of action could be through the inhibition of the Smad pathway.
authors: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Taiwan.
authors: Hsin-Ying
authors: HY
authors: Chuang
authors: Lean-Teik
authors: LT
authors: Ng
authors: Liang-Tzung
authors: LT
authors: Lin
authors: Jung-San
authors: JS
authors: Chang
authors: Jen-Yang
authors: JY
authors: Chen
authors: Ta-Chen
authors: TC
authors: Lin
authors: Chun-Ching
authors: CC
authors: Lin
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D003603:Cytotoxins / Q000494:pharmacology / Q000627:therapeutic use; D005638:Fruit; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D047348:Hydrolyzable Tannins / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051896:Smad Proteins, Receptor-Regulated / Q000378:metabolism; D029766:Terminalia / Q000737:chemistry*; D053773:Transforming Growth Factor beta1
chemical_list: D001578:Benzopyrans; D024042:Collagen Type I; D024061:Collagen Type III; D003603:Cytotoxins; D005960:Glucosides; D047348:Hydrolyzable Tannins; D010936:Plant Extracts; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D051896:Smad Proteins, Receptor-Regulated; D053773:Transforming Growth Factor beta1; C103481:chebulinic acid; C076178:chebulagic acid; D003094:Collagen