Inhibition of human organic cation transporters by the alkaloids matrine and oxymatrine

Human organic cation transporters (hOCTs; SLC22) are expressed in many organs, including intestine, liver, kidney, heart and brain, where they contribute to the absorption, distribution, and elimination of endogenous and exogenous substances. The alkaloids matrine and oxymatrine are widely used in herbal medicine for the treatment of cancer, as well as viral, and cardiac diseases. Their physicochemical properties indicated that they are potential inhibitors for hOCTs, leading to drug–drug interactions in vivo. Therefore, we assessed the inhibitory effects of matrine and oxymatrine on the function of hOCT1 (SLC22A1), hOCT2 (SLC22A2) and hOCT3 (SLC22A3) using stably transfected transporter-expressing cells. At 100-fold excess, oxymatrine exhibited marked inhibition of hOCT1-mediated substrate uptake (p < 0.05), while matrine failed to produce significant inhibition on hOCT1. The IC50 value for oxymatrine on hOCT1 was estimated as 513 ± 132 μM. While there was no significant inhibition of hOCT2 or hOCT3 at 100-fold excess, oxymatrine and matrine showed 42% and 88% inhibition of hOCT3-mediated substrate uptake at 3 and 6 mM, respectively. Considering the potential intestinal lumen and reported plasma concentrations of matrine and oxymatrine, these data suggest that drug–drug interactions may occur during hOCT1-mediated hepatic and renal uptake and during hOCT3-mediated intestinal absorption.

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