Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture

Abstract

Quercetin and related flavonoids are naturally occurring polyphenolic compounds with multiple pharmacological activities. Using cultured human umbilical vein endothelial cells, we investigated the effects of quercetin on endothelin (ET-1) and tissue plasminogen activator (t-PA) release induced by thrombin. We observed that when endothelial cells pretreated with 5 or 50 μM of quercetin were incubated for 4 and 24 h with thrombin, ET-1 concentration-dependently decreased ( n=6, P<0.01, at 4 h IC 50=1.54 μM, at 24 h IC 50=2.78 μM). Under the same experimental conditions, quercetin significantly increased t-PA ( n=6, P<0.01, at 4 h EC 50=0.71 μM and at 24 hrs EC 50=0.74 μM). In the same preparation, we evaluated prostacyclin (PGI 2) release, induced by thrombin activated platelets, as determined by a 6-Keto-PGF 1α radioimmunoassay. Following the treatment of cultured endothelial cells with activated platelets, the concentration of 6-Keto-PGF 1α was significantly increased ( P<0.01). Quercetin (1, 5, and 20 μM) inhibited PGI 2, in a concentration-dependent manner ( n=6, P<0.05). Our data indicate that quercetin modulates the release of ET-1, t-PA, and PGI 2 from vascular endothelial cells.