(S)--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)--gingerol on these TGF-β-mediated proteoglycan changes to explore its potential as an anti-atherosclerotic agent.Methods
Purified (S)--gingerol was assessed for its effects on proteoglycan synthesis by [35S]-sulfate incorporation into glycosaminoglycan chains and [35S]-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)--gingerol on TGF-β signalling by assessment of the phosphorylation of Smads and Akt by western blotting.Key findings
(S)--Gingerol concentration-dependently inhibited TGF-β-stimulated proteoglycan core protein synthesis, and this was not secondary to inhibition of total protein synthesis. (S)--Gingerol inhibited biglycan mRNA expression. (S)--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)--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)--gingerol in inhibiting TGF-β responses.