title: Inhibition of human organic cation transporters by the alkaloids matrine and oxymatrine.
abstract: 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 6mM, 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.
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA. Electronic address: wangl4@vcu.edu.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, University of Cologne, Gleueler Strasse 24, 50931 Cologne, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Gründemann
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA 23298, USA.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Sweet
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D001692:Biological Transport; D002412:Cations / Q000378:metabolism*; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D007408:Intestinal Absorption; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D027702:Organic Cation Transporter 1 / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D029909:Sophora / Q000737:chemistry*; D014162:Transfection; D000093842:Matrines
chemical_list: D000470:Alkaloids; D002412:Cations; D027702:Organic Cation Transporter 1; D010936:Plant Extracts; D011807:Quinolizines; C037573:oxymatrine; D000093842:Matrines
keywords: Drug–drug interaction; Matrine (PubChem CID: 91466); Oxymatrine (PubChem CID: 114850); SLC22; Solute carrier; Uptake transporters