32-3 |
Angiogenic and anti-angiogenic properties of natural polyphenolic antioxidants |
D. BAGCHI, School of Pharmacy & Health Professions, Creighton Univ. Medical Center, 2500 California Plaza, Criss B59E, Omaha, NE 68178 Edible berry anthocyanins, grape seed proanthocyanidins, and resveratrol demonstrate a broad spectrum of pharmacological, and therapeutic properties. Angiogenesis plays a central role in wound healing, as well as modulates tumor growth and cancer metastases. Anti-angiogenic approaches to prevent and treat cancer represent a priority area in investigative tumor biology. Vascular endothelial growth factor (VEGF) is the most prevalent, efficacious and long-term signal in stimulating angiogenesis in wounds, as well as the vascularization of tumors. An oxidized milieu in the wound micro-environment favors the expression of VEGF and supports the healing process. We demonstrated that grape seed proanthocyanidins with 5000 ppm resveratrol (GSPE) potentiated both H2O2-and TNFa-induced VEGF expression in human keratinocytes. GSPE accelerated wound contraction and closure, which was seen from day 1 in male BalbC mice. Enhanced formation of epidermis and connective tissue repair was also observed. Histological evaluation demonstrated more extensive granulation tissue below the reepithelialization tissue. 4-hydroxynonenal and glutathione redox status demonstrated enhanced tissue oxidation. Six edible berry extracts including blueberry, bilberry, elderberry, cranberry, raspberry and strawberry, and a novel combination (OptiBerry) were evaluated. Blueberry and OptiBerry demonstrated higher ORAC values as compared to GSPE. Berry samples significantly inhibited both H2O2 and TNFa-induced VEGF expression. This effect was not shared by other antioxidants such as a-tocopherol or GSPE, but was shared by catachin and rutin. Matigel assay using human dermal microvascular endothelial cells showed that edible berries and OptiBerry impaired angiogenesis. Thus, OptiBerry may be used as a chemotherapeutic agent. We hypothesize that the structure activity relationship between key constituents may play a major role in VEGF regulatory properties. The results demonstrate that natural antioxidants exhibit a broad spectrum of properties and health benefits.
Session 32, Angiogenesis and functional foods
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