Interaction of natural dietary and herbal anionic compounds and flavonoids with human organic anion transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11)

Abstract

Active components of complementary/alternative medicines and natural supplements are often anionic compounds and flavonoids. As such, organic anion transporters (OATs) may play a key role in their pharmacokinetic and pharmacological profiles, and represent sites for adverse drug-drug interactions. Therefore, we assessed the inhibitory effects of nine natural products, including flavonoids (catechin and epicatechin), chlorogenic acids (1,3- and 1,5-dicaffeoylquinic acid), phenolic acids (ginkgolic acids (13: 0), (15: 1), and (17: 1)), and the organic acids ursolic acid and 18β-glycyrrhetinic acid, on the transport activity of the human OATs, hOAT1 (SLC22A6), hOAT3 (SLC22A8), and hOAT4 (SLC22A11). Four compounds, 1,3- and 1,5-dicaffeoylquinic acid, ginkgolic acid (17: 1), and 18β-glycyrrhetinic acid, significantly inhibited hOAT1-mediated transport (50 M inhibitor versus 1 M substrate). Five compounds, 1,3- and 1,5-dicaffeoylquinic acid, ginkgolic acids (15: 1) and (17: 1), and epicatechin, significantly inhibited hOAT3 transport under similar conditions. Only catechin inhibited hOAT4. Dose-dependency studies were conducted for 1,3-dicaffeoylquinic acid and 18β-glycyrrhetinic acid on hOAT1, and ICvalues were estimated as 1.2 ± 0.4 M and 2.7 ± 0.2 M, respectively. These data suggest that 1,3-dicaffeoylquinic acid and 18β-glycyrrhetinic acid may cause significant hOAT1-mediated DDIs in vivo; potential should be considered for safety issues during use and in future drug development. © 2013 Li Wang and Douglas H. Sweet.