Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions
文献类型：期刊论文
| 作者 | Olaleye, Olajide E; Niu, Wei; Du, Fei-Fei; Wang, Feng-Qing; Xu, Fang; Pintusophon, Salisa; Lu, Jun-Lan; Yang, Jun-Ling ; Li, Chuan
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| 刊名 | Acta pharmacologica Sinica
 |
| 出版日期 | 2018-10-16 |
| ISSN号 | 1745-7254 |
| DOI | 10.1038/s41401-018-0173-9 |
| 文献子类 | Article |
| 英文摘要 | ShenMai, an intravenous injection prepared from steamed Panax ginseng roots (Hongshen) and Ophiopogon japonicus roots (Maidong), is used as an add-on therapy for coronary artery disease and cancer; saponins are its bioactive constituents. Since many saponins inhibit human organic anion-transporting polypeptides (OATP)1B, this investigation determined the inhibition potencies of circulating ShenMai saponins on the transporters and the joint potential of these compounds for ShenMai-drug interaction. Circulating saponins and their pharmacokinetics were characterized in rats receiving a 30-min infusion of ShenMai at 10 mL/kg. Inhibition of human OATP1B1/1B3 and rat Oatp1b2 by the individual saponins was investigated in vitro; the compounds' joint inhibition was also assessed in vitro and the data was processed using the Chou-Talalay method. Plasma protein binding was assessed by equilibrium dialysis. Altogether, 49 saponins in ShenMai were characterized and graded into: 10-100 μmol/day (compound doses from ShenMai; 7 compounds), 1-10 μmol/day (17 compounds), and <1 μmol/day (25 compounds, including Maidong ophiopogonins). After dosing, circulating saponins were protopanaxadiol-type ginsenosides Rb, Rb, Rc, Rd, Ra, Rg, Ra, and Ra, protopanaxatriol-type ginsenosides Rg, Re, Rg, and Rf, and ginsenoside Ro. The protopanaxadiol-type ginsenosides exhibited maximum plasma concentrations of 2.1-46.6 μmol/L, plasma unbound fractions of 0.4-1.0% and terminal half-lives of 15.6-28.5 h (ginsenoside Rg, 1.9 h), while the other ginsenosides exhibited 0.1-7.7 μmol/L, 20.8-99.2%, and 0.2-0.5 h, respectively. The protopanaxadiol-type ginsenosides, ginsenosides without any sugar attachment at C-20 (except ginsenoside Rf), and ginsenoside Ro inhibited OATP1B3 more potently (IC, 0.2-3.5 µmol/L) than the other ginsenosides (≥22.6 µmol/L). Inhibition of OATP1B1 by ginsenosides was less potent than OATP1B3 inhibition. Ginsenosides Rb, Rb, Rc, Rd, Ro, Ra, Re, and Rg likely contribute the major part of OATP1B3-mediated ShenMai-drug interaction potential, in an additive and time-related manner. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266561]  |
| 专题 | 新药研究国家重点实验室 上海药物代谢研究中心 科研与新药推进处 |
| 通讯作者 | Yang, Jun-Ling; Li, Chuan |
| 作者单位 | State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China |
| 推荐引用方式 GB/T 7714 | Olaleye, Olajide E,Niu, Wei,Du, Fei-Fei,et al. Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions[J]. Acta pharmacologica Sinica,2018. |
| APA | Olaleye, Olajide E.,Niu, Wei.,Du, Fei-Fei.,Wang, Feng-Qing.,Xu, Fang.,...&Li, Chuan.(2018).Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions.Acta pharmacologica Sinica. |
| MLA | Olaleye, Olajide E,et al."Multiple circulating saponins from intravenous ShenMai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions".Acta pharmacologica Sinica (2018). |
入库方式： OAI收割
来源：上海药物研究所
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