title: A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells.
abstract: We investigated the effects of the flavonols kaempferol and quercetin on the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), endothelial cell selectin (E-selectin), inducible NO synthase (iNOS) and cyclo-oxygenase-2 (COX-2), and on the activation of the signalling molecules NF-kappaB and activator protein-1 (AP-1), induced by a cytokine mixture in cultured human umbilical vein endothelial cells. Inhibition of reactive oxygen and nitrogen species generation did not differ among both flavonols at 1 micromol/l but was significantly stronger for kaempferol at 5-50 micromol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (5-50 micromol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 micromol/l), ICAM-1 (50 micromol/l) and E-selectin (50 micromol/l) expression was also observed. Expression of adhesion molecules was always more strongly inhibited in kaempferol-treated than in quercetin-treated cells. The inhibitory effect on iNOS and COX-2 protein level was stronger for quercetin at 5-50 micromol/l. The effect of kaempferol on NF-kappaB and AP-1 binding activity was weaker at high concentrations (50 micromol/l) as compared with quercetin. The present study indicates that differences exist in the modulation of pro-inflammatory genes and in the blockade of NF-kappaB and AP-1 by kaempferol and quercetin. The minor structural differences between both flavonols determine differences in their anti-inflammatory properties and in their efficiency in inhibiting signalling molecules.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) and Institute of Biomedicine, University of León, León 24071, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Crespo
authors.forename: María V
authors.initials: MV
authors.lastname: García-Mediavilla
authors.forename: Belén
authors.initials: B
authors.lastname: Gutiérrez
authors.forename: Sonia
authors.initials: S
authors.lastname: Sánchez-Campos
authors.forename: María J
authors.initials: MJ
authors.lastname: Tuñón
authors.forename: Javier
authors.initials: J
authors.lastname: González-Gallego
mesh_terms: D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000032:analysis; D016207:Cytokines / Q000494:pharmacology*; D019040:E-Selectin / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D044949:Kaempferols / Q000494:pharmacology*; D016328:NF-kappa B / Q000032:analysis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011794:Quercetin / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000032:analysis; D014471:Umbilical Veins; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; D044949:Kaempferols; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C006552:kaempferol; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2