Abstract

Curcumin and quercetin are natural compounds with a wide spectrum of activities, including antioxidant and anticancer activities. In this study, the combined effect of the two compounds was investigated, with special emphasis on the pharmacokinetics of curcumin by the quercetin-induced changes in the albumin binding of curcumin. We evaluated the effect of quercetin on the binding of curcumin to albumin and on the uptake of curcumin into the cells of the human colon carcinoma cell line WiDr. In addition, we also investigated changes in the in vivo pharmacokinetics of curcumin and curcumin sulfate (the major metabolite of curcumin) coadministered with quercetin. We found that quercetin inhibited the binding of curcumin to albumin and increased the uptake of curcumin into WiDr cells, the human colon carcinoma cell. The quercetin-induced increased uptake (1.6-fold) of curcumin into WiDr cells was also confirmed by an ex vivo study. The in vivo pharmacokinetics of curcumin showed obvious changes when it was coadministered with quercetin, with the significantly lower plasma concentration and greater biliary excretion of curcumin and curcumin sulfate. The present study suggests that quercetin could enhance the cellular uptake of curcumin and modulate in vivo pharmacokinetics of curcumin, and it could be related to albumin-binding interaction.