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dc.contributor.authorWarner, Emily F
dc.contributor.authorZhang, Qingzhi
dc.contributor.authorRaheem, K. Saki
dc.contributor.authorO'Hagan, David
dc.contributor.authorO’Connell, Maria A.
dc.contributor.authorKay, Colin D
dc.date.accessioned2016-03-25T13:30:03Z
dc.date.available2016-03-25T13:30:03Z
dc.date.issued2016-03-01
dc.identifier.citationWarner , E F , Zhang , Q , Raheem , K S , O'Hagan , D , O’Connell , M A & Kay , C D 2016 , ' Common phenolic metabolites of flavonoids, but not their unmetabolized precursors, reduce the secretion of vascular cellular adhesion molecules by human endothelial cells ' , Journal of Nutrition , vol. 146 , no. 3 , pp. 465-473 . https://doi.org/10.3945/jn.115.217943en
dc.identifier.issn0022-3166
dc.identifier.otherPURE: 241583141
dc.identifier.otherPURE UUID: c228fc38-d246-46bd-bd28-e3a16ed298ec
dc.identifier.otherRIS: urn:EE644A6DF21060ADCB239DF8A93C6ED8
dc.identifier.otherScopus: 84960417297
dc.identifier.otherWOS: 000372198200001
dc.identifier.otherORCID: /0000-0002-0510-5552/work/68281240
dc.identifier.urihttp://hdl.handle.net/10023/8489
dc.descriptionThis study was supported by funding from the UK Biotechnology and Biological Sciences Research Council Diet and Health Research Industry Club (BBSRC-DRINC) (BB/I006028/1).en
dc.description.abstractBackground: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. Objective: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Method: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM–100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Results: Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (−17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2–36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2–54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no activity toward sVCAM-1, suggesting no additive activity at 1 μM. Conclusions: The present findings suggest that metabolism of flavonoids increases their vascular efficacy, resulting in a diversity of structures of varying bioactivity in human endothelial cells.
dc.format.extent9
dc.language.isoeng
dc.relation.ispartofJournal of Nutritionen
dc.rightsThis is an open access article distributed under the CC-BY license (http://creativecommons.org/licenses/by/3.0/).en
dc.subjectPolyphenolen
dc.subjectVCAM-1en
dc.subjectEndothelialen
dc.subjectInflammationen
dc.subjectPhase II conjugateen
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subject.lccQDen
dc.titleCommon phenolic metabolites of flavonoids, but not their unmetabolized precursors, reduce the secretion of vascular cellular adhesion molecules by human endothelial cellsen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.3945/jn.115.217943
dc.description.statusPeer revieweden


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