Upregulation of oxidant-induced VEGF expression in cultured keratinocytes by a grape seed proanthocyanidin extract

Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. The wound site is rich in oxidants such as hydrogen peroxide mostly contributed by neutrophils and macrophages. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. This study provides first evidence showing that natural extracts such as grape seed proanthocyanidin extract containing 5000 ppm resveratrol (GSPE) facilitates oxidant-induced VEGF expression in keratinocytes. Using a ribonuclease protection assay (RPA), the ability of GSPE to regulate oxidant-induced changes in several angiogenesis-related genes were studied. While mRNA responses were studied using RPA, VEGF protein release from cells to the culture medium was studied using ELISA. Pretreatment of HaCaT keratinocytes with GSPE upregulated both hydrogen peroxide as well as TNF-alpha-induced VEGF expression and release. The current results suggest that GSPE may have beneficial therapeutic effects in promoting dermal wound healing and other related skin disorders.