A comparison of the effects of kaempferol and quercetin on cytokine-induced pro-inflammatory status of cultured human endothelial cells

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 oil the activation of the signalling molecules NF-kappa B 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 mu nol/l but was significantly stronger for kaempferol at 5-50 mu mol/l. Supplementation with increasing concentrations of kaempferol substantially attenuate(] the increase induced by the cytokine mixture in VCAM-1 (10-50 mu mol/l). ICAM-1 (50 mu mol/l) and E-selectin (5-50 mu mol/l) expression. A significantly inhibitory effect of quercetin on VCAM-1 (10-50 mu mol/l), ICAM-1 (50 mu mol/l) and E-selectin (50 mu mol/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 mu mol/l. The effect of kaempferol on NF-kappa B and AP-1 binding activity was weaker at high concentrations (50 mu mol/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-kappa B 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.