title: In vitro inhibition of human cGMP-specific phosphodiesterase-5 by polyphenols from red grapes.
abstract: 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.
authors.affiliation: Department of Pharmacological Sciences, Faculty of Pharmacy, University of Milan, via Balzaretti 9, 20133 Milan, Italy. mario.dellagli@unimi.it
authors.forename: Mario
authors.initials: M
authors.lastname: Dell'Agli
authors.forename: Germana V
authors.initials: GV
authors.lastname: Galli
authors.forename: Urska
authors.initials: U
authors.lastname: Vrhovsek
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mattivi
authors.forename: Enrica
authors.initials: E
authors.lastname: Bosisio
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000872:Anthocyanins / Q000032:analysis / Q000494:pharmacology; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry*; D005960:Glucosides; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D014664:Vasodilation; D027843:Vitis / Q000737:chemistry*; D014920:Wine / Q000032:analysis
chemical_list: D000872:Anthocyanins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005960:Glucosides; D010636:Phenols; D059808:Polyphenols; C458419:malvidin-3-glucoside; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; C517381:PDE5A protein, human