| Autor: |
Cerezo López, Ana Belén, Winterbone, Mark S., Moyle, Christina W.A., Needs, Paul W., Kroon, Paul A. |
| Přispěvatelé: |
Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
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| Popis: |
Scope We recently reported potent inhibition of VEGF signalling by two flavanols at sub-micromolar concentrations, mediated by direct binding of the flavanols to VEGF. The aim of this study was to quantify the inhibitory potency and binding affinity of a wide range of dietary polyphenols and determine the structural requirements for VEGF inhibition. Methods and results The concentration of polyphenol required to cause 50% inhibition (IC50) of VEGF-dependent VEGFR-2 activation in HUVECS was determined after pretreating VEGF with polyphenols at various concentations. Binding affinities and binding sites on VEGF were predicted using in-silico modelling. Ellagic acid and 15 flavonoids had IC50 values ≤10 μM while 28 other polyhenols were weak/non-inhibitors. Structural features associated with potent inhibition included 3-galloylation, C-ring C2=C3, total OH, B-ring catechol, C-ring 3-OH of flavonoids. Potency was not associated with polyphenol hydrophobicity. There was a strong correlation between potency of inhibition and binding affinities, and all polyphenols were predicted to bind to a region on VEGF involved in VEGFR-2 binding. Conclusion Specific polyphenols bind directly to a discrete region of VEGF and inhibit VEGF signalling, and this potentially explains the associations between consumption of these polyphenols and CVD risk. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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