title: Interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3).
abstract: The present study aimed to investigate the interaction characteristics of flavonoids with human organic anion transporter 1 (hOAT1) and 3 (hOAT3). Five flavonoids (morin, silybin, naringin, naringenin and quercetin) were selected and their interaction characteristics with hOAT1 and hOAT3 were examined in MDCK cells overexpressing hOAT1 or hOAT3. Among tested flavonoids, morin and silybin exhibited significant inhibition effects on the cellular uptake of [3H]-para-aminohippuric acid ([3H]-PAH) in MDCK-hOAT1 cells with Ki of 0.46 microM and 24 microM, respectively, while all the tested flavonoids appeared to be less interactive with hOAT3 compared to hOAT1. A kinetic study suggested that morin and silybin inhibited hOAT1-mediated cellular uptake of [3H]-PAH in a competitive manner. Furthermore, morin and silybin were translocated by hOAT1 across the cellular membrane. In conclusion, the present study identified some of flavonoids as a new class of hOAT1 inhibitors, suggesting a potential for flavonoid-drug interactions via the modulation of hOAT1 activity.
authors.affiliation: School of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Soon Sun
authors.initials: SS
authors.lastname: Hong
authors.forename: Kisoo
authors.initials: K
authors.lastname: Seo
authors.forename: Sung-Chul
authors.initials: SC
authors.lastname: Lim
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D004347:Drug Interactions; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D005419:Flavonoids / Q000378:metabolism*; D006801:Humans; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism; D014162:Transfection
chemical_list: D005419:Flavonoids; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D011084:Polycyclic Aromatic Hydrocarbons; C114338:organic anion transport protein 3; D004970:Estrone; C017296:estrone sulfate