dc.creator | Cerezo López, Ana Belén | es |
dc.creator | Winterbone, Mark S. | es |
dc.creator | Moyle, Christina W.A. | es |
dc.creator | Needs, Paul W. | es |
dc.creator | Kroon, Paul A. | es |
dc.date.accessioned | 2022-09-14T09:44:52Z | |
dc.date.available | 2022-09-14T09:44:52Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Cerezo López, A.B., Winterbone, M.S., Moyle, C.W.A., Needs, P.W. y Kroon, P.A. (2015). Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Molecular Nutrition & Food Research, 59 (11), 2119-2131. | |
dc.identifier.issn | 1613-4133 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137052 | |
dc.description.abstract | 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. | es |
dc.format | application/pdf | es |
dc.format.extent | 13 p. | es |
dc.language.iso | eng | es |
dc.publisher | Wiley | es |
dc.relation.ispartof | Molecular Nutrition & Food Research, 59 (11), 2119-2131. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Angiogenesis | es |
dc.subject | Atherosclerosis | es |
dc.subject | Binding affinity | es |
dc.subject | Flavonoids | es |
dc.subject | Phenolics | es |
dc.title | Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Nutrición y Bromatología, Toxicología y Medicina Legal | es |
dc.relation.publisherversion | https://dx.doi.org/10.1002/mnfr.201500407 | es |
dc.identifier.doi | 10.1002/mnfr.201500407 | es |
dc.journaltitle | Molecular Nutrition & Food Research | es |
dc.publication.volumen | 59 | es |
dc.publication.issue | 11 | es |
dc.publication.initialPage | 2119 | es |
dc.publication.endPage | 2131 | es |