Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells.
Adhesion of circulating monocytes to vascular endothelial cells, a critical step in both inflammation and atherosclerosis, is mediated by cross-linkage of adhesion molecules expressed on the surface of both cell types. Dietary flavonoids have been shown to have anti-inflammatory properties, decreasing the expression of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. However, flavonoids are efficiently metabolised during absorption and the forms reaching the systemic circulation are glucuronidated, sulphated and methylated. Most previous in vitro studies of the effects of flavonoids have used the parent compounds at concentrations far higher than those physiologically achievable. We investigated the ability of quercetin and its human metabolites, at physiological concentrations (2 micromol/L and 10 micromol/L), to attenuate the inflammation-induced upregulated expression of VCAM-1, ICAM-1 and of the chemokine, monocyte chemoattractant protein-1 (MCP-1), in human umbilical vein endothelial cells (HUVECs), at the protein and transcript levels. Quercetin treatment reduced the inflammation-induced over-expression of VCAM-1 and ICAM-1 (protein and transcript) in HUVECs. Quercetin also inhibited MCP-1 gene expression. However, quercetin 3'-sulfate, quercetin 3-glucuronide and 3'-methylquercetin 3-glucuronide (isorhamnetin 3-glucuronide) generally exhibited either a reduced ability to inhibit the expression of these molecules compared with the parent aglycone or had no effect. However, all three metabolites inhibited VCAM-1 cell surface expression at 2 micromol/L. These results indicate that both quercetin and its metabolites, at physiological concentrations, can inhibit the expression of key molecules involved in monocyte recruitment during the early stages of atherosclerosis.
Tribolo
Sandra
S
Phytochemicals and Health Programme, Institute of Food Research, Norwich Research Park, Norwich NR4 7UA, UK.
Lodi
Federica
F
Connor
Carol
C
Suri
Sunita
S
Wilson
Vincent G
VG
Taylor
Moira A
MA
Needs
Paul W
PW
Kroon
Paul A
PA
Hughes
David A
DA
D050197:Atherosclerosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D009000:Monocytes / Q000473:pathology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011794:Quercetin