Malvidin-3-glucoside protects endothelial cells up-regulating endothelial NO synthase and inhibiting peroxynitrite-induced NF-kB activation

Abstract

Anthocyanins are the most abundant flavonoid constituents of fruits and vegetables and several epidemiological studies suggest that the consumption of these compounds protect against several diseases, including vascular disorders. Previously, we have reported that anthocyanins are able to counteract peroxynitrite-induced apoptotic effects in endothelial cells through inhibition of several crucial signaling cascades, upstream and downstream of mitochondria. Following these studies, here we investigated possible effects of malvidin-3-glucoside, one of the main dietary anthocyanins, on NO bioavailability and on peroxynitrite-induced NF-kB activation in the same cell model. Our results show that treatment of bovine arterial endothelial cells with malvidin-3-glucoside up-regulated eNOS mRNA, leading to the enhancement of eNOS activity and NO production, an effect even greater when cells were further stimulated with peroxynitrite. On the other hand, in these activated endothelial cells, malvidin-3-glucoside suppressed pro-inflammatory mediators, namely iNOS expression/NO biosynthesis, COX-2 expression and IL-6 production, through inhibition of NF-kB activation. These findings suggest a potential role of malvidin-3-glucoside in NO balance and in inhibition of pro-inflammatory signaling pathways, supporting its benefits in cardiovascular health and pointing to anthocyanins as a promising tool for development of functional foods and nutraceuticals to improve endothelial function.