Multiple circulating saponins from intravenous Shenmai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions : = Multiple circulating saponins from intravenous Shenmai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions
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)1 B, 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 Shen Mai at 10 m L·kg~(-1). Inhibition of human OATP1 B1/1 B3 and rat Oatp1 b2 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·d-1(compound doses from Shenmai;7 compounds), 1-10 μmol · d~(-1)(17 compounds), and<1 μmol · d~(-1)(25 compounds, including Maidong ophiopogonins). After dosing, circulating saponins were protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, Rd, Ra1, Rg3,Ra2, and Ra3, protopanaxatriol-type ginsenosides Rg1,Re, Rg2, and Rf, and ginsenoside Ro. The protopanaxadioltype ginsenosides exhibited maximum plasma concentrations of 2.1-46.6 μmol·L~(-1), plasma unbound fractions of 0.4%-1.0% and terminal half-lives of 15.6-28.5 h(ginsenoside Rg3, 1.9 h), while the other ginsenosides exhibited 0.1-7.7 μmol·L~(-1), 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__(50), 0.2-3.5 μmol · L~(-1)) than the other ginsenosides(≥22.6 μmol·L~(-1)). Inhibition of OATP1B1 by ginsenosides was less potent than OATP1B3 inhibition. Ginsenosides Rb1, Rb2, Rc, Rd, Ro, Ra1, Re, and Rg2 likely contribute the major part of OATP1B3-mediated Shenmai-drug interaction potential, in an additive and time-related manner..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019-10-15 2019 |
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| Erschienen: |
2019-10-15 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2019 |
|---|---|
| Enthalten in: |
Zhong guo yao li xue yu du li xue za zhi - (2019), 10 vom: 15. Okt., Seite 760 Original Letters: Enthalten in 中国药理学与毒理学杂志 (DE-600)2989809-2 (DE-600)2989809-2 北京市 |
| Reihe: |
China Academic Journals (CAJ), E, 医药卫生科技 = Medicine & Public Health |
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| Sprache: |
Chinesisch |
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| Weiterer Titel: |
Multiple circulating saponins from intravenous Shenmai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions |
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| Beteiligte Personen: |
Olajide E OLALEYE [VerfasserIn] |
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| Links: |
oversea.cnki.net [lizenzpflichtig] |
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| Anmerkungen: |
Author info:Olajide E OLALEYE;NIU Wei;DU Fei-fei;WANG Feng-qing;XU Fang;Salisa PINTUSOPHON;LU Jun-lan;YANG Jun-ling;LI Chuan;State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
CAJ64583517X |
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| 245 | 1 | 0 | |a Multiple circulating saponins from intravenous Shenmai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions |b = Multiple circulating saponins from intravenous Shenmai inhibit OATP1Bs in vitro: potential joint precipitants of drug interactions |
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| 520 | |a 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)1 B, 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 Shen Mai at 10 m L·kg~(-1). Inhibition of human OATP1 B1/1 B3 and rat Oatp1 b2 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·d-1(compound doses from Shenmai;7 compounds), 1-10 μmol · d~(-1)(17 compounds), and<1 μmol · d~(-1)(25 compounds, including Maidong ophiopogonins). After dosing, circulating saponins were protopanaxadiol-type ginsenosides Rb1, Rb2, Rc, Rd, Ra1, Rg3,Ra2, and Ra3, protopanaxatriol-type ginsenosides Rg1,Re, Rg2, and Rf, and ginsenoside Ro. The protopanaxadioltype ginsenosides exhibited maximum plasma concentrations of 2.1-46.6 μmol·L~(-1), plasma unbound fractions of 0.4%-1.0% and terminal half-lives of 15.6-28.5 h(ginsenoside Rg3, 1.9 h), while the other ginsenosides exhibited 0.1-7.7 μmol·L~(-1), 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__(50), 0.2-3.5 μmol · L~(-1)) than the other ginsenosides(≥22.6 μmol·L~(-1)). Inhibition of OATP1B1 by ginsenosides was less potent than OATP1B3 inhibition. Ginsenosides Rb1, Rb2, Rc, Rd, Ro, Ra1, Re, and Rg2 likely contribute the major part of OATP1B3-mediated Shenmai-drug interaction potential, in an additive and time-related manner. | ||
| 610 | 2 | 4 | |a State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
| 650 | 4 | |a 中药学、方剂学 | |
| 650 | 4 | |a 中医 | |
| 650 | 4 | |a 医药、卫生 | |
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