Laboratory of Clinical Pharmaceutics and Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-0812, Japan.
Biopharm Drug Dispos. 2014 Apr;35(3):173-82. doi: 10.1002/bdd.1882. Epub 2014 Jan 14.
Quercetin-3-rhamnoglucoside (rutin) has a wide spectrum of biochemical and pharmacological activities. Rutin is absorbed mainly in its unmetabolized form. Organic anion transporting polypeptide (OATP) 2B1 is a major uptake transporter in the intestine. Thus, it is important for the prevention of adverse events to understand drug interactions mediated by OATP2B1 in the absorption process. This study assessed the effect of rutin on transport by OATP2B1. Rutin stimulated the uptake of estrone-3-sulfate (E-3-S), taurocholic acid (TCA), cholic acid (CA) and rosuvastatin by OATP2B1, but not p-coumaric acid or ferulic acid. The EC50 of rutin for transport by OATP2B1 was 2.32 μm. The Km value of E-3-S for OATP2B1 in the presence of rutin (9.21 μm) was almost the same as that in the absence of rutin (8.53 μm). On the other hand, the Vmax of E-3-S transport by OATP2B1 in the presence of rutin (270 pmol/mg protein/min) was 1.2-fold higher than that in the absence of rutin (218 pmol/mg protein/min). Moreover, the expression level of OATP2B1 on the cell membrane was increased by treatment with rutin for 5 min without alteration of the total OATP2B1 expression level. Moreover, the increase in the localization of OATP2B1 at the cell surface was detected by the immunocytochemistry. The stimulatory effect of rutin is a little weak but may affect the absorption of OATP2B1 substrates, because rutin is taken daily in foods and its intestinal concentration would reach the stimulatory range of OATP2B1.
槲皮素-3-鼠李糖苷（芦丁）具有广泛的生化和药理活性。芦丁主要以未代谢的形式被吸收。有机阴离子转运多肽（OATP）2B1 是肠道中的主要摄取转运体。因此，了解吸收过程中 OATP2B1 介导的药物相互作用对于预防不良反应非常重要。本研究评估了芦丁对 OATP2B1 转运的影响。芦丁刺激雌酮-3-硫酸盐（E-3-S）、牛磺胆酸（TCA）、胆酸（CA）和瑞舒伐他汀的摄取由 OATP2B1 介导，但对对香豆酸或阿魏酸没有作用。芦丁对 OATP2B1 转运的 EC50 为 2.32 μm。芦丁存在时 E-3-S 对 OATP2B1 的 Km 值（9.21 μm）几乎与芦丁不存在时相同（8.53 μm）。另一方面，芦丁存在时 E-3-S 由 OATP2B1 转运的 Vmax（270 pmol/mg 蛋白/min）比芦丁不存在时高 1.2 倍（218 pmol/mg 蛋白/min）。此外，芦丁处理 5 分钟可增加 OATP2B1 细胞膜上的表达水平，而不改变总 OATP2B1 表达水平。此外，通过免疫细胞化学检测到 OATP2B1 在细胞表面的定位增加。芦丁的刺激作用虽然较弱，但可能会影响 OATP2B1 底物的吸收，因为芦丁每天都存在于食物中，其肠道浓度可能达到 OATP2B1 的刺激范围。
