Effects of natural products on the function of human organic anion transporting polypeptide 1B1

1. In this study, the effects of 136 naturally occurring products, which have been reported to play important roles in modification of Cytochrome P450 (CYP450) activities, on the uptake of estrone-3-sulfate (E3S), a typical OATP1B1 substrate, were evaluated using human embryonic kidney 293 cells stably expressing OATP1B1. 2. At a concentration of 100 mu M, 42 natural products inhibited OATP1B1-mediated [H-3] E3S uptake by more than 50%, and five of them significantly inhibited OATP1B1-mediated [H-3] E3S by more than 80% with the following rank order of potency: quercetin > astragaloside IV > icariin > glycyrrhizic acid > ginsenoside Rc. Inhibitory effects of these natural products on OATP1B1 activity were in a concentration-dependent manner. 11 natural compounds were found exhibiting greater than 50% inhibition at 30 mu M with IC50 values ranging from 14.6 +/- 3.3 to 28.5 +/- 3.0 mu M. 3. In conclusion, our data suggest that modification of OATP1B1 transport activity by these natural occurring products may be a mechanism for natural product-drug interactions in humans.