title: Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells.
abstract: METHODS
  In vitro and in vivo studies suggest that dietary anthocyanins modulate cardiovascular disease risk; however, given anthocyanins extensive metabolism, it is likely that their degradation products and conjugated metabolites are responsible for this reported bioactivity.
  
  
  RESULTS
  Human vascular endothelial cells were stimulated with either oxidized LDL (oxLDL) or cluster of differentiation 40 ligand (CD40L) and cotreated with cyanidin-3-glucoside and 11 of its recently identified metabolites, at 0.1, 1, and 10 μM concentrations. Protein and gene expression of IL-6 and VCAM-1 was quantified by ELISA and RT-qPCR. In oxLDL-stimulated cells the parent anthocyanin had no effect on IL-6 production, whereas numerous anthocyanin metabolites significantly reduced IL-6 protein levels; phase II conjugates of protocatechuic acid produced the greatest effects (>75% reduction, p ≤ 0.05). In CD40L-stimulated cells the anthocyanin and its phase II metabolites reduced IL-6 protein production, where protocatechuic acid-4-sulfate induced the greatest reduction (>96% reduction, p ≤ 0.03). Similarly, the anthocyanin and its metabolites reduced VCAM-1 protein production, with ferulic acid producing the greatest effect (>65% reduction, p ≤ 0.04).
  
  
  CONCLUSIONS
  These novel data provide evidence to suggest that anthocyanin metabolites are bioactive at physiologically relevant concentrations and have the potential to modulate cardiovascular disease progression by altering the expression of inflammatory mediators.
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors: Hiren P
authors: HP
authors: Amin
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors: Charles
authors: C
authors: Czank
authors: Department of Life Sciences, Faculty of Science and Technology, University of Westminster, London, UK.
authors: Saki
authors: S
authors: Raheem
authors: School of Chemistry St. Andrews University, Fife, Scotland, UK.
authors: Qingzhi
authors: Q
authors: Zhang
authors: School of Chemistry St. Andrews University, Fife, Scotland, UK.
authors: Nigel P
authors: NP
authors: Botting
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors: Aedín
authors: A
authors: Cassidy
authors: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors: Colin D
authors: CD
authors: Kay
mesh_terms: D000872:Anthocyanins / Q000494:pharmacology*; D023201:CD40 Ligand / Q000378:metabolism*; D003373:Coumaric Acids / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D005960:Glucosides / Q000494:pharmacology*; D020719:Glucuronides / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000872:Anthocyanins; D003373:Coumaric Acids; D005960:Glucosides; D020719:Glucuronides; D062385:Hydroxybenzoates; C508600:IL6 protein, human; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; C462279:cyanidin-3-O-beta-glucopyranoside; C099252:oxidized low density lipoprotein; D023201:CD40 Ligand; C009091:protocatechuic acid; C004999:ferulic acid
keywords: Adhesion molecule; Cyanidin-3-glucoside; Cytokine; Inflammation; Metabolites