Inhibitory actions of bilberry anthocyanidins on angiogenesis

Abstract

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.

Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits

“…Anthocyanin-rich extracts of several berries (wild blueberry, bilberry, cranberry, elderberry, and strawberry) significantly suppress hydrogen peroxide and TNF-α-induced vascular endothelial growth factor (VEGF) expression in HaCaT cells (human keratinocytes) [117]. Bilberry anthocyanidins (delphinidin, cyanidin, and malvidin) are also reported to inhibit VEGF-induced tube formation in a co-culture of human umbilical vein endothelial cells and fibroblasts [118]. …”

Alternative Medicine in Diabetes - Role of Angiogenesis, Oxidative Stress, and Chronic Inflammation

“…Herbal extracts have shown VEGF-inhibitory effects. Anthocyanidins, which are constituents of bilberry anthocyanosides, are able to inhibit VEGF-induced tube formation [46]. They could thus be applied to prevent VEGF-induced endothelial injury.…”

“…They are able to inhibit ROS production and thus protect endothelial cells and even pancreatic islets from oxidative injury [46,64,73,74]. Li et al showed that streptozotocin-induced diabetic mice treated with cinnamon polyphenols showed significantly downregulated blood glucose and insulin levels in serum.…”

“…Constituents from anthocyanosides, in particular anthocyanidins, possess strong antioxidant properties. They were able to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals in human umbilical vein endothelial cells [46], and to reduce ROS levels and oxidative DNA damage in human colon cells [72].…”

“…Further beneficial effects comprise the stabilization of collagen fibers, promotion of collagen biosynthesis [119], decrease of capillary permeability and fragility by inhibiting VEGF-induced injury [46,120], and inhibition of platelet aggregation [121]. Moreover, anthocyanosides and bilberry leaf constituents prevent the release and synthesis of pro-inflammatory compounds, such as histamine, prostaglandins, and leukotrienes [122].…”