In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes

J Agric Food Chem. 2005 Mar 23;53(6):1960-5. doi: 10.1021/jf048497+.


A moderate consumption of red wine may reduce the risk of cardiovascular diseases via wine-derived phenolic compounds. A variety of biological mechanisms have been proposed for wine-derived phenolic compounds including nitric oxide-mediated vasorelaxation. This study examined whether the vasodilating effect of wine-derived phenolic compounds was associated with the inhibition of phosphodiesterases (PDEs) and, in particular, PDE5. For this purpose, human recombinant PDE5A1 isoform was prepared by expression of the full-length cDNA of PDE5A1 into COS-7 cells. Red wine and the extracts from grape skin inhibited PDE5A1 activity, whereas the seed extracts had a negligible effect. The mixture of anthocyanins inhibited the enzyme activity (IC50 = 11.6 microM), with malvidin-3-O-beta-glucoside (IC50 = 35.4 microM) and malvidin (IC50 = 24.9 microM) the most potent among the monoglucosides and aglycons, respectively. trans-Resveratrol and trans-piceid exhibited negligible effects, whereas hydroxycinnamates were completely inactive. These results indicate that polyphenols-induced vasorelaxation may also be sustained by smooth muscle PDE inhibition by anthocyanins present in red wines and grapes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • Anthocyanins / analysis
  • Anthocyanins / pharmacology
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Enzyme Inhibitors / pharmacology*
  • Flavonoids / pharmacology*
  • Fruit / chemistry*
  • Glucosides
  • Phenols / pharmacology*
  • Polyphenols
  • Vasodilation
  • Vitis / chemistry*
  • Wine / analysis


  • Anthocyanins
  • Enzyme Inhibitors
  • Flavonoids
  • Glucosides
  • Phenols
  • Polyphenols
  • malvidin-3-glucoside
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human