Physiologically relevant metabolites of quercetin have no effect on adhesion molecule or chemokine expression in human vascular smooth muscle cells.
Dietary flavonoids have been shown to have a number of anti-inflammatory properties, including decreasing the expression of adhesion molecules. Flavonoids however, are metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulfated and methylated. Most previous studies of the effects of flavonoids have used the parent compounds rather than the metabolites found in blood plasma and we have recently shown that metabolites of quercetin can retain some of the anti-inflammatory properties of the parent aglycone when used to treat human umbilical endothelial cells (HUVEC). Using both physiologically achievable (2 microM) and supraphysiological (10 microM) concentrations, we investigated the ability of quercetin and its predominant human metabolites to attenuate the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) in human umbilical artery smooth muscle cells (HUASMC) activated by tumor necrosis factor-alpha (TNFalpha). Quercetin was able to reduce TNFalpha-induced upregulation of VCAM-1, ICAM-1 and MCP-1 at both the protein and transcript (mRNA) level in HUASMC. However the quercetin metabolites, quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide, had no effect on TNFalpha-induced up regulation of adhesion molecule or chemokine expression, at either concentration tested. These data do not support the notion that the vascular anti-inflammatory effects of quercetin consumption are mediated through effects on smooth muscle cells.
Winterbone
Mark S
MS
Phytochemicals and Health Programme, Institute of Food Research, Norwich Research Park, Norwich, Norfolk, NR4 7UA, UK. mark.winterbone@bbsrc.ac.uk
Tribolo
Sandra
S
Needs
Paul W
PW
Kroon
Paul A
PA
Hughes
David A
DA
D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D018925:Chemokines / Q000502:physiology; D044948:Flavonols / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014469:Umbilical Arteries / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D044948:Flavonols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C531389:quercetin 3'-sulfate; C443401:quercetin 3-O-glucuronide; C047368:3-methylquercetin; D018799:Intercellular Adhesion Molecule-1; D011794:Quercetin