Inhibitory actions of bilberry anthocyanidins on angiogenesis

The aim of this study was to examine the antiangiogenic properties and antioxidant activities (a) of the main anthocyanidins (delphinidin, cyanidin and malvidin) found as constituents in Vaccinium myrtillus (bilberry) anthocyanosides (VMA) and (b) of N-acetyl-L-cysteine (NAC). Each of these anthocyanidins concentration-dependently inhibited vascular endothelial growth factor (VEGF)-induced tube formation in a co-culture of human umbilical vein endothelial cells (HUVECs) and fibroblasts, the effect of each anthocyanidin being significant at 3 and/or 10 microM, while NAC significantly inhibited such tube formation at 1 microM (the only concentration tested). Moreover, each anthocyanidin (0.3-10 microM) and NAC (1-1000 microM) concentration-dependently scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. The inhibitory effects against angiogenesis were similar among the anthocyanidins, as were those against the DPPH radical. Moreover, their radical-scavenging effects were induced by concentrations that were at or below those that induced their antiangiogenic effects. These findings indicate that the inhibitory effect of VMA on angiogenesis may depend on those of its main constituent anthocyanidins (delphinidin, cyanidin and malvidin), presumably via antioxidant effects.