title: (S)-[6]-Gingerol inhibits TGF-β-stimulated biglycan synthesis but not glycosaminoglycan hyperelongation in human vascular smooth muscle cells.
abstract: OBJECTIVE
  (S)-[6]-Gingerol is under investigation for a variety of therapeutic uses. Transforming growth factor (TGF)-β stimulates proteoglycan synthesis, leading to increased binding of low-density lipoproteins, which is the initiating step in atherosclerosis. We evaluated the effects of (S)-[6]-gingerol on these TGF-β-mediated proteoglycan changes to explore its potential as an anti-atherosclerotic agent.
  
  
  METHODS
  Purified (S)-[6]-gingerol was assessed for its effects on proteoglycan synthesis by [(35) S]-sulfate incorporation into glycosaminoglycan chains and [(35) S]-Met/Cys incorporation into proteoglycans and total proteins in human vascular smooth muscle cells. Biglycan level was assessed by real-time quantitative polymerase chain reactions and the effects of (S)-[6]-gingerol on TGF-β signalling by assessment of the phosphorylation of Smads and Akt by western blotting.
  
  
  RESULTS
  (S)-[6]-Gingerol concentration-dependently inhibited TGF-β-stimulated proteoglycan core protein synthesis, and this was not secondary to inhibition of total protein synthesis. (S)-[6]-Gingerol inhibited biglycan mRNA expression. (S)-[6]-Gingerol did not inhibit TGF-β-stimulated glycosaminoglycan hyperelongation or phosphorylation of Smad 2, in either the carboxy terminal or linker region, or Akt phosphorylation.
  
  
  CONCLUSIONS
  The activity of (S)-[6]-gingerol to inhibit TGF-β-stimulated biglycan synthesis suggests a potential role for ginger in the prevention of atherosclerosis or other lipid-binding diseases. The signalling studies indicate a novel site of action of (S)-[6]-gingerol in inhibiting TGF-β responses.
authors.affiliation: Discipline of Pharmacy, School of Medical Sciences and Diabetes Complications Group, Health Innovations Research Institute, RMIT University, Bundoora.
authors.forename: Danielle
authors.initials: D
authors.lastname: Kamato
authors.forename: Hossein
authors.initials: H
authors.lastname: Babaahmadi Rezaei
authors.forename: Robel
authors.initials: R
authors.lastname: Getachew
authors.forename: Lyna
authors.initials: L
authors.lastname: Thach
authors.forename: Daniel
authors.initials: D
authors.lastname: Guidone
authors.forename: Narin
authors.initials: N
authors.lastname: Osman
authors.forename: Basil
authors.initials: B
authors.lastname: Roufogalis
authors.forename: Colin C
authors.initials: CC
authors.lastname: Duke
authors.forename: Van Hoan
authors.initials: VH
authors.lastname: Tran
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Little
mesh_terms: D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control; D058578:Biglycan / Q000096:biosynthesis*; D015153:Blotting, Western; D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D058578:Biglycan; D002396:Catechols; D005233:Fatty Alcohols; D006025:Glycosaminoglycans; D012333:RNA, Messenger; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C007845:gingerol; D051057:Proto-Oncogene Proteins c-akt