Protective effects of quercetin and its metabolites on endothelial dysfunction in rat aorta

Abstract

Epidemiological studies have reported an inverse association between dietary flavonoid intake and mortality for ischemic heart disease. Quercetin is the most abundant flavonoid in the diet, but it is not present in plasma as a free form. The main metabolites of quercetin in human plasma are: quercetin-3-glucuronide, quercetin-3′-sulphate, isorhamnetin-3-glucuronide and 4′-glucuronide. In this study, we have characterised the vascular effects of these conjugates on rat aorta. We found that these metabolites lacked a direct vasodilator effect. Moreover, they did not suffer auto-oxidation, did not generate free radicals, and did not inhibit the biological activity of NO. However, these metabolites protected the biological activity of NO and reversed the endothelial dysfunction induced by an inhibitor of superoxide dismutase or by NADPH-induced NADPH oxidase activation. These data indicate for the first time that the conjugated metabolites could be responsible for the in vivo protective activity of quercetin on endothelial dysfunction and blood pressure. Supported by AGL2004-06685/ALI and SAF2005-03770