Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya 4678603, Japan.
Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan.
J Ethnopharmacol. 2018 Mar 25;214:153-159. doi: 10.1016/j.jep.2017.12.016. Epub 2017 Dec 14.
The use of herbal medicines has become popular worldwide, and the information on drug interactions between herbal medicines and chemical drugs is needed.
We screened the inhibitory effects of crude drugs used in Kampo medicines used in Japan on organic anion-transporting polypeptide (OATP) 2B1 to predict potential interactions between Kampo medicines and chemical drugs used together.
We chose 98 kinds of crude drugs frequently used as ingredients of Kampo formulations in Japan and prepared their boiling water extracts. We then screened their inhibitory effects on OATP2B1 by measuring the uptake of estrone 3-sulphate (E3S) by HEK293 cells stably expressing OATP2B1.
At the concentration of 100µg/ml, the extracts prepared from 12 kinds of crude drugs, Scuteralliae Radix, Arecae Semen, Aurantii Fructus Immaturus, Perillae Herba, Panacis Japonici Rhizoma, Moutan Cortex, Polygalae Radix, Rhei Rhizoma, Cannabis Fructus, Chrysanthemi Flos, Eriobotryae Folium, and Querci Cortex, suppressed the function of OATP2B1 by less than 20%. The extract of bofutsushosan, a representative Kampo formulation, inhibited OATP2B1 function with sufficient levels to suppress absorption of OATP2B1 substrates in clinics. We further evaluated the inhibitory effects of several ingredients containing Rhei Rhizoma, Perillae Herba, and Moutan Cortex on OATP2B1.
Because of crude drugs used in Kampo medicines might suppress absorption of OATP2B1 substrates, these results may contribute to the safe and effective use of Kampo medicine in clinics. A list of abbreviations: EC, (-)-epicatechin; ECG, epicatechin gallate; EGC, epigallocatechin; EGCG, Epigallocatechin gallate; FBS, fetal bovine serum; grapefruit juice; HEK293, Human embryonic kidney; IC The half inhibitory concentration; OATP, organic anion-transporting polypeptide; β-PGG, penta-O-galloyl-β-D-glucose; t.i.d, 3 times a day.
草药的使用在全球范围内变得流行，因此需要了解草药与化学药物之间的药物相互作用信息。
我们筛选了日本汉方药中常用草药的粗提物对有机阴离子转运多肽（OATP）2B1 的抑制作用，以预测汉方药与同时使用的化学药物之间的潜在相互作用。
我们选择了日本汉方制剂中常用的 98 种草药作为成分，并制备了它们的沸水提取物。然后，我们通过测量稳定表达 OATP2B1 的 HEK293 细胞摄取雌酮 3-硫酸盐（E3S）来筛选这些提取物对 OATP2B1 的抑制作用。
在 100µg/ml 浓度下，从 12 种草药的提取物中，Scuteralliae Radix、Arecae Semen、Aurantii Fructus Immaturus、Perillae Herba、Panacis Japonici Rhizoma、Moutan Cortex、Polygalae Radix、Rhei Rhizoma、Cannabis Fructus、Chrysanthemi Flos、Eriobotryae Folium 和 Querci Cortex 抑制了 OATP2B1 的功能，抑制率低于 20%。一种代表性的汉方制剂——保妇康栓的提取物对 OATP2B1 功能的抑制作用足以抑制 OATP2B1 底物的吸收。我们进一步评估了 Rhei Rhizoma、Perillae Herba 和 Moutan Cortex 中的几种成分对 OATP2B1 的抑制作用。
由于汉方药中的草药可能会抑制 OATP2B1 底物的吸收，因此这些结果可能有助于汉方药在临床中的安全有效使用。缩略语列表：EC，（-）-儿茶素；ECG，表儿茶素没食子酸酯；EGC，表没食子儿茶素；EGCG，表没食子儿茶素没食子酸酯；FBS，胎牛血清；葡萄柚汁；HEK293，人胚肾；IC 半抑制浓度；OATP，有机阴离子转运多肽；β-PGG，五-O-没食子酰基-β-D-葡萄糖；tid，每日 3 次。
