RESUMEN
The major dietary flavonol quercetin, which has been shown to improve endothelial function and decrease blood pressure, is extensively metabolized during absorption. This study examined the relative abilities of quercetin and its human metabolites to modulate the expression of eNOS and ET-1, which are involved in regulating endothelial homeostasis. Quercetin aglycone significantly reduced both eNOS protein and gene expression in HUVEC, mirroring the effects of the pro-inflammatory cytokine TNFα. In the presence of TNFα the aglycone caused further reductions in eNOS, whereas the metabolites were without effect in either TNFα-stimulated or unstimulated cells. ET-1 expression was significantly reduced by quercetin in both TNFα-stimulated or unstimulated HUVECs. The metabolites had no effect on ET-1 expression with the exception of quercetin-3'-sulfate, which caused a moderate increase in TNFα-stimulated cells. These results suggest that metabolic transformation of quercetin prevents it from causing a potentially deleterious decrease in eNOS in endothelial cells.