Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3
文献类型：期刊论文
| 作者 | Jiang, Rongrong1,2; Dong, Jiajia2; Li, Xiuxue2; Du, Feifei2; Jia, Weiwei2; Xu, Fang2; Wang, Fengqing2; Yang, Junling2 ; Niu, Wei2; Li, Chuan1,2,3
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| 刊名 | BRITISH JOURNAL OF PHARMACOLOGY
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| 出版日期 | 2015-02 |
| 卷号 | 172期号:4页码:1059-1073 |
| ISSN号 | 0007-1188 |
| DOI | 10.1111/bph.12971 |
| 文献子类 | Article |
| 英文摘要 | Background and PurposeGinsenosides are bioactive saponins derived from Panax notoginseng roots (Sanqi) and ginseng. Here, the molecular mechanisms governing differential pharmacokinetics of 20(S)-protopanaxatriol-type ginsenoside Rg(1), ginsenoside Re and notoginsenoside R-1 and 20(S)-protopanaxadiol-type ginsenosides Rb-1, Rc and Rd were elucidated. Experimental ApproachInteractions of ginsenosides with human and rat hepatobiliary transporters were characterized at the cellular and vesicular levels. A rifampin-based inhibition study in rats evaluated the in vivo role of organic anion-transporting polypeptide (Oatp)1b2. Plasma protein binding was assessed by equilibrium dialysis. Drug-drug interaction indices were calculated to estimate potential for clinically relevant ginsenoside-mediated interactions due to inhibition of human OATP1Bs. Key ResultsAll the ginsenosides were bound to human OATP1B3 and rat Oatp1b2 but only the 20(S)-protopanaxatriol-type ginsenosides were transported. Human multidrug resistance-associated protein (MRP)2/breast cancer resistance protein (BCRP)/bile salt export pump (BSEP)/multidrug resistance protein-1 and rat Mrp2/Bcrp/Bsep also mediated the transport of the 20(S)-protopanaxatriol-type ginsenosides. Glomerular-filtration-based renal excretion of the 20(S)-protopanaxatriol-type ginsenosides was greater than that of the 20(S)-protopanaxadiol-type counterparts due to differences in plasma protein binding. Rifampin-impaired hepatobiliary excretion of the 20(S)-protopanaxatriol-type ginsenosides was effectively compensated by the renal excretion in rats. The 20(S)-protopanaxadiol-type ginsenosides were potent inhibitors of OATP1B3. Conclusion and ImplicationsDifferences in hepatobiliary and in renal excretory clearances caused markedly different systemic exposure and different elimination kinetics between the two types of ginsenosides. Caution should be exercised with the long-circulating 20(S)-protopanaxadiol-type ginsenosides as they could induce hepatobiliary herb-drug interactions, particularly when patients receive long-term therapies with high-dose i.v. Sanqi or ginseng extracts. |
| WOS关键词 | ANION-TRANSPORTING POLYPEPTIDES ; HEART-FAILURE ; ENDOTHELIAL-CELLS ; PANAX-NOTOGINSENG ; HUMAN LIVER ; CARDIOMYOCYTE HYPERTROPHY ; ARRIVE GUIDELINES ; HEPATIC-UPTAKE ; SAPONINS ; RECEPTOR |
| 资助项目 | National Natural Science Fund of China for Distinguished Young Scholars[30925044] ; National Science & Technology Major Project of China 'Key New Drug Creation and Manufacturing Program'[2009ZX09304-002] ; National Basic Research Program of China[2012CB518403] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000348507700008 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276658]  |
| 专题 | 上海药物代谢研究中心 科研与新药推进处 |
| 通讯作者 | Li, Chuan |
| 作者单位 | 1.Univ Chinese Acad Sci, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Rongrong,Dong, Jiajia,Li, Xiuxue,et al. Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3[J]. BRITISH JOURNAL OF PHARMACOLOGY,2015,172(4):1059-1073. |
| APA | Jiang, Rongrong.,Dong, Jiajia.,Li, Xiuxue.,Du, Feifei.,Jia, Weiwei.,...&Li, Chuan.(2015).Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3.BRITISH JOURNAL OF PHARMACOLOGY,172(4),1059-1073. |
| MLA | Jiang, Rongrong,et al."Molecular mechanisms governing different pharmacokinetics of ginsenosides and potential for ginsenoside-perpetrated herb-drug interactions on OATP1B3".BRITISH JOURNAL OF PHARMACOLOGY 172.4(2015):1059-1073. |
入库方式： OAI收割
来源：上海药物研究所
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