Membrane organic anion-transporting polypeptides (OATPs) are responsible for the drug transmembrane transport within the human body. The function of OATP2B1 transporter can be inhibited by various natural compounds. Despite increased research interest in soya as a part of human diet, the effect of its active components to interact with hOATP2B1 has not been elucidated in a complex extent. This in vitro study examined the inhibitory effect of main soy isoflavones (daidzin, daidzein, genistin, genistein, glycitin, glycitein, biochanin A, formononetin) and their metabolites formed in vivo (S-equol, O-desmethylangolensin) towards human OATP2B1 transporter. MDCKII cells overexpressing hOATP2B1 were employed to determine quantitative inhibitory parameters of the tested compounds and to analyze mechanism/s of the inhibitory interaction. The study showed that aglycones of soy isoflavones and the main biologically active metabolite S-equol were able to significantly inhibit hOATP2B1-mediated transport. The Ki values for most of aglycones range from 1 to 20 μM. In contrast, glucosides did not exhibit significant inhibitory effect. The kinetic analysis did not indicate a uniform type of inhibition towards the hOATP2B1 although predominant mechanism of inhibition seemed to be competitive. These findings may suggest that tested soy isoflavones and their metabolites might affect transport of xenobiotics including drugs across tissue barriers via hOATP2B1.
Keywords: Drug transporter; Flavonoids; OATP; SLCO; Soy isoflavones.