EXTENSIVE BINDING OF THE BIOFLAVONOID QUERCETIN TO HUMAN PLASMA-PROTEINS

Although the bioflavonoids, a large group of polyphenolic natural prod ucts, exert chemopreventive effects in cardiovascular disease and canc er, there is little information about the disposition of these dietary components in man. The objective of this study was to investigate the plasma-protein binding of the most abundant bioflavonoid, quercetin, using C-14-labelled quercetin. An ultracentrifugation assay (170 000 g for 16 h at 20 degrees C) was shown to sediment plasma proteins. Bind ing of quercetin to normal plasma was extensive (99.1 +/- 0.5%, mean /- s.d., n = 5). The unbound fraction varied as much as 6-fold, 0.3-1. 8%, between subjects. This high binding was independent of quercetin c oncentration over the range 1.5-15 mu M (0.5-5 mu g mL(-1)). Human ser um albumin was the primary protein responsible for the binding of quer cetin in plasma (99.4 +/- 0.1%). Binding by al-acid glycoprotein (39.2 +/- 0.5%) and very-low-density lipoproteins (< 0.5% of total querceti n) did not make substantial contributions to overall plasma binding. T he equilibrium association constant for the binding of quercetin to se rum albumin was 267 +/- 33 x 10(3) M-1 (n = 15). Thermodynamic data fo r the binding of quercetin to serum albumin indicated spontaneous, end othermic association. Displacement studies suggested that in man the ' IIA' subdomain binding site of human serum albumin was the primary bin ding site for quercetin. Association of quercetin with erythrocytes wa s significantly (P < 0.001) reduced by plasma protein binding. These d ata indicate poor cellular availability of quercetin because of its ex tensive binding to plasma proteins.