Context: Organic anion-transporting polypeptide 2B1 (OATP2B1) which is highly expressed in enterocytes and hepatocytes could be a key determinant for the intestinal absorption and hepatic uptake of its substrate drugs. Natural products are commonly used in traditional Chinese medicine, foods, and beverages. Objective: The objective of this study is to determine the OATP2B1-mediated drug interactions that could occur between natural products and OATP2B1 substrate drugs. Materials and methods: Human OATP2B1 was transiently expressed in human embryonic kidney (HEK293) cells and characterized by immunofluorescence, Western blot, and uptake assay. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods for detecting OATP2B1 substrates estrone-3-sulfate (E3S) and three statins had been developed and were employed to investigate the effects of 27 frequently used natural products on the function of OATP2B1. Uptake of 5 lM E3S and 1 lM statins in the absence or presence of natural products was measured at 37 C for 2 min with empty vector-and OATP2B1-transfected HEK293 cells. The IC 50 values of inhibitors for OATP2B1-mediated 5 lM E3S uptake were determined. Results: Our results showed that mulberrin, scutellarin, quercetin, and glycyrrhetinic acid were strong inhibitors of OATP2B1-mediate E3S uptake with IC 50 values being 1.8, 2.0, 7.5, and 13.0 lM, which were comparable with their plasma concentrations in clinical trials. They also inhibited OATP-mediated uptake of atorvastatin, fluvastatin, and rosuvastatin. These results indicated that clinically relevant drug interactions could occur between these natural compounds and OATP2B1 substrate drugs. Discussion and conclusion: The information obtained from this study might be helpful to predict and to avoid potential OATP2B1-mediated drug interactions.

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