Malvidin, a red wine polyphenol, modulates mammalian myocardial and coronary performance and protects the heart against ischemia/reperfusion injury

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.