title: Estrogen-like effects of wine extracts on nitric oxide synthesis in human endothelial cells.
abstract: Endothelial dysfunction frequently ensues during the climacteric due to hormonal and metabolic changes. Non-pharmacological interventions such as lifestyle and dietary modifications are emerging as valuable strategies to counteract the cardiovascular consequences of ageing. A number of chemical components of wine, including alcohol and some polyphenols, are known to be active on the vessels. However, the molecular mechanisms through which they modulate endothelial function are largely unclear. The aim of this study was to investigate the effects of non-alcoholic wine fractions from five different wines on the synthesis of nitric oxide (NO) via the expression and enzymatic activation of the endothelial nitric oxide synthase (eNOS) in human endothelial cells. All non-alcoholic fractions studied increased NO synthesis, although with different potencies. All wine extracts maximally enhanced NO production at doses in the range achieved with a moderate wine intake, with decreasing effects with further increases of the dose. Interestingly, a part of these actions was recruited via estrogen receptors (ERs). Within the polyphenols with known binding activity for ERs contained in the tested wines, resveratrol, epicatechin, syringic acid, apigenin, malvidin and ellagic acid were largely responsible for eNOS activation. These findings show that some of the non-alcoholic components of wine enhance the production of NO by the vessels acting on ERs, and suggest that a moderate intake of wine may benefit the cardiovascular system through estrogen-like effects.
authors.affiliation: Department of Reproductive Medicine and Child Development, Division of Gynaecology and Obstetrics, University of Pisa, Pisa, Italy. tommaso.simoncini@med.unipi.it
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.forename: Elena
authors.initials: E
authors.lastname: Lenzi
authors.forename: Alfred
authors.initials: A
authors.lastname: Zöchling
authors.forename: Santhosh
authors.initials: S
authors.lastname: Gopal
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Goglia
authors.forename: Eleonora
authors.initials: E
authors.lastname: Russo
authors.forename: Kinga
authors.initials: K
authors.lastname: Polak
authors.forename: Elena
authors.initials: E
authors.lastname: Casarosa
authors.forename: Alois
authors.initials: A
authors.lastname: Jungbauer
authors.forename: Alessandro D
authors.initials: AD
authors.lastname: Genazzani
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Genazzani
mesh_terms: D000428:Alcohol Drinking; D002460:Cell Line; D002979:Climacteric; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005638:Fruit; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*; D014920:Wine
chemical_list: D004967:Estrogens; D010936:Plant Extracts; D059808:Polyphenols; D011960:Receptors, Estrogen; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III