title: Inhibitory effect of medicinal plant-derived carboxylic acids on the human transporters hOAT1, hOAT3, hOATP1B1, and hOATP2B1.
abstract: A significant number of organic carboxylic acids have been shown to influence the absorption and distribution of drugs mediated by organic anion transporters (OATs). In this study, uptake experiments were performed to assess the inhibitory effects of cinnamic acid, ferulic acid, oleanolic acid, deoxycholic acid, and cynarin on hOAT1, hOAT3, hOATP1B1, and hOATP2B1. After a drug-drug interaction (DDI) investigation, cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were found and validated to inhibit hOAT1 in a competitive manner, and deoxycholic acid was found to be an inhibitor of all four transporters. The apparent 50% inhibitory concentrations of cinnamic acid, ferulic acid, deoxycholic acid, and cynarin were estimated to be 133.87, 3.69, 90.03 and 6.03 μmol·L(-1) for hOAT1, respectively. The apparent 50% inhibitory concentrations of deoxycholic acid were estimated to be 9.57 μmol·L(-1) for hOAT3, 70.54 μmol·L(-1) for hOATP1B1, and 168.27 μmol·L(-1) for hOATP2B1. Because cinnamic acid, ferulic acid, and cynarin are ingredients of food or food additives, the present study suggests there are new food-drug interactions to be disclosed. In addition, deoxycholic acid may be used as a probe for studying the correlation of OATs and OATPs.
authors.affiliation: School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China; State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Zhi-Yu
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Duan-Yun
authors.initials: DY
authors.lastname: Si
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. Electronic address: yixl@tjipr.com.
authors.forename: Xiu-Lin
authors.initials: XL
authors.lastname: Yi
authors.affiliation: State Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China. Electronic address: liuchangxiao@163.com.
authors.forename: Chang-Xiao
authors.initials: CX
authors.lastname: Liu
mesh_terms: D002264:Carboxylic Acids / Q000494:pharmacology*; D002934:Cinnamates / Q000494:pharmacology; D003373:Coumaric Acids / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000494:pharmacology*; D004032:Diet; D004347:Drug Interactions; D057809:HEK293 Cells; D006801:Humans; D027362:Organic Anion Transport Protein 1 / Q000037:antagonists & inhibitors; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D002264:Carboxylic Acids; D002934:Cinnamates; D003373:Coumaric Acids; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D010936:Plant Extracts; D003840:Deoxycholic Acid; C029010:cinnamic acid; C100257:cynarine; C004999:ferulic acid
keywords: Food-drug interactions; Transport; hOAT1; hOAT3; hOATP1B1; hOATP2B1