Potent inhibition of VEGFR-2 activation by tight binding of green tea epigallocatechin gallate and apple procyanidins to VEGF: Relevance to angiogenesis

Christina W. A. Moyle and colleagues from the Institute of Food Research (IFR, UK) have demonstrate for the first time that VEGF is a key molecular target for specific polyphenols found in tea, apples and cocoa, which potently inhibit VEGF signalling and angiogenesis at physiological concentrations. These data provide a plausible mechanism that links bioactive compounds in food with their beneficial effects.

Vascular endothelial growth factor (VEGF) is a pro-angiogenic growth factor that is inhibited by dietary polyphenolic compounds. Excessive concentrations of VEGF drive angiogenesis –formation of new blood vessels when there is an imbalance between angiogenic growth factors– and cause complications, such as increased growth of tumours and atherosclerotic plaques.

Previous studies have shown that epigallocatechin gallate, found in green tea, and procyanidins, found in apples,inhibit VEGF-mediated VEGFR-2 phosphorylation by interacting directly with VEGF and reducing binding to the receptor.

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  1. Polyphenol-induced inhibition of VEGF-induced VEGFR-2 activation occurs at nano molarpolyphenol concentrations and follows bi-phasic inhibition kinetics
  2. Exposure of VEGF to epigallocatechin gallate or procyanid in oligomers inhibits binding of VEGF to human umbilical vein endothelial cells expressing VEGFR-2
  3. VEGFR-2 signalling was inhibited completely at 1 µM (polyphenols), but the downstream endothelial nitric oxide synthase was still active via the PI3K/Akt signalling pathway