title: Malvidin, a red wine polyphenol, modulates mammalian myocardial and coronary performance and protects the heart against ischemia/reperfusion injury.
abstract: A moderate red wine consumption and a colored fruit-rich diet protect the cardiovascular system, thanks to the presence of several polyphenols. Malvidin-3-0-glucoside (malvidin), an anthocyanidine belonging to polyphenols, is highly present in red grape skin and red wine. Its biological activity is poorly characterized, although a role in tumor cell inhibition has been found. To analyze whether and to which extent, like other food-derived polyphenols, malvidin affects the cardiovascular function, in this study, we have performed a quantitative analysis by high-performance liquid chromatography of polyphenolic content of red grape skins extract, showing that it contains a high malvidin amount (63.93 ±12.50 mg/g of fresh grape skin). By using the isolated and Langendorff perfused rat heart, we found that the increasing doses (1-1000 ng/ml) of the extract induced positive inotropic and negative lusitropic effects associated with coronary dilation. On the same cardiac preparations, we observed that malvidin (10(-10)-10(-6) mol/L) elicited negative inotropism and lusitropism and coronary dilation. Analysis of mechanism of action revealed that malvidin-dependent cardiac effects require the activation of the phosphatidylinositol 3-kinase (PI3K)/nitric oxide (NO)/cGMP/PKG pathway and are associated with increased intracellular cGMP and the phosphorylation of endothelial NO synthase (eNOS), PI3K-AKT, ERK1/2, and GSK-3β. AKT and eNOS phosphorylation was confirmed in human umbilical vein endothelial cell. We also found that malvidin act as a postconditioning agent, being able to elicit cardioprotection against ischemia/reperfusion damages. Our results show the cardioactivity of polyphenols-rich red grape extracts and indicate malvidin as a new cardioprotective principle. This is of relevance not only for a better clarification of the beneficial cardiovascular effects of food-derived polyphenols but also for nutraceutical research.
authors.affiliation: Department of Cell Biology, University of Calabria, Arcavacata di Rende, CS, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Quintieri
authors.forename: Noemi
authors.initials: N
authors.lastname: Baldino
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Filice
authors.forename: Lucia
authors.initials: L
authors.lastname: Seta
authors.forename: Antonio
authors.initials: A
authors.lastname: Vitetti
authors.forename: Bruno
authors.initials: B
authors.lastname: Tota
authors.forename: Bruno
authors.initials: B
authors.lastname: De Cindio
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cerra
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014920:Wine / Q000032:analysis*
chemical_list: D000872:Anthocyanins; C065861:malvidin; D052250:Nitric Oxide Synthase Type III; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3