Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic.
Naunyn Schmiedebergs Arch Pharmacol. 2018 Oct;391(10):1063-1071. doi: 10.1007/s00210-018-1528-y. Epub 2018 Jun 22.
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 K 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.
膜有机阴离子转运多肽（OATPs）负责人体内药物的跨膜转运。OATP2B1 转运蛋白的功能可被多种天然化合物抑制。尽管人们对大豆作为人类饮食的一部分越来越感兴趣，但大豆的活性成分与 hOATP2B1 相互作用的影响尚未在复杂程度上得到阐明。本体外研究考察了主要大豆异黄酮（大豆苷、大豆苷元、染料木苷、染料木素、黄豆黄苷、黄豆黄素、大豆苷元、芒柄花素）及其在体内形成的代谢物（S--equol、O-去甲安哥拉紫檀素）对人 OATP2B1 转运蛋白的抑制作用。采用过表达 hOATP2B1 的 MDCKII 细胞来确定测试化合物的定量抑制参数，并分析抑制相互作用的机制。研究表明，大豆异黄酮的苷元和主要生物活性代谢物 S-Equol 能够显著抑制 hOATP2B1 介导的转运。大多数苷元的 K 值在 1 到 20 μM 之间。相比之下，糖苷没有表现出明显的抑制作用。虽然抑制的主要机制似乎是竞争性的，但动力学分析并未表明对 hOATP2B1 的抑制类型是一致的。这些发现可能表明，测试的大豆异黄酮及其代谢物可能会影响包括药物在内的外源性物质通过 hOATP2B1 穿过组织屏障的转运。
