a1 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) and Institute of Biomedicine, University of León, León 24071, Spain
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-κB 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 μmol/l but was significantly stronger for kaempferol at 5–50 μmol/l. Supplementation with increasing concentrations of kaempferol substantially attenuated the increase induced by the cytokine mixture in VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (5–50 μmol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10–50 μmol/l), ICAM-1 (50 μmol/l) and E-selectin (50 μmol/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 μmol/l. The effect of kaempferol on NF-κB and AP-1 binding activity was weaker at high concentrations (50 μmol/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-κB 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.
(Received October 09 2007)
(Revised January 31 2008)
(Accepted February 04 2008)
(Online publication April 08 2008)
Abbreviations: AP-1, activator protein-1; COX-2, cyclo-oxygenase-2; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; E-selectin, endothelial cell selectin; HUVEC, human umbilical vein endothelial cells; ICAM-1, intercellular adhesion molecule-1; iNOS, inducible NO synthase; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; RNS, reactive nitrogen species; ROS, reactive oxygen species; Tris, 2-amino-2-(hydroxymethyl)propane-1,3-diol; VCAM-1, vascular cell adhesion molecule-1