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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.
AuthorsAnna Maria Quintieri, Noemi Baldino, Elisabetta Filice, Lucia Seta, Antonio Vitetti, Bruno Tota, Bruno De Cindio, Maria Carmela Cerra, Tommaso Angelone
JournalThe Journal of nutritional biochemistry (J Nutr Biochem) Vol. 24 Issue 7 Pg. 1221-31 (Jul 2013) ISSN: 1873-4847 [Electronic] United States
PMID23266283 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Anthocyanins
  • malvidin
  • Nitric Oxide Synthase Type III
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
Topics
  • Animals
  • Anthocyanins (pharmacology)
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Glycogen Synthase Kinase 3 (metabolism)
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • MAP Kinase Signaling System
  • Male
  • Myocardial Reperfusion Injury (enzymology, physiopathology, prevention & control)
  • Nitric Oxide Synthase Type III (metabolism)
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt (metabolism)
  • Rats
  • Rats, Wistar
  • Wine (analysis)

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