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学科主题: 物理化学
题名: Ginsenoside Metabolites Inhibit P-Glycoprotein In Vitro and In Situ Using Three Absorption Models
作者: Li, Na1, 2;  Wang, Dandan1, 2;  Ge, Guangbo1;  Wang, Xiuli3;  Liu, Yong1;  Yang, Ling1
通讯作者: 杨凌
关键词: ginseng ;  ginsenoside ;  intestinal metabolism ;  P-glycoprotein ;  inhibitor
刊名: PLANTA MEDICA
发表日期: 2014-03-01
DOI: 10.1055/s-0033-1360334
卷: 80, 期:4, 页:290-296
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Plant Sciences ;  Chemistry, Medicinal ;  Pharmacology & Pharmacy
研究领域[WOS]: Plant Sciences ;  Pharmacology & Pharmacy
英文摘要: P-glycoprotein, an ATP-dependent transporter expressed in the gastrointestinal tract and tumor cells, mediates the efflux transport of multiple drugs. Inhibition or induction of P-glycoprotein by herbal ingredients can lead to herb-drug interactions and thus influence the activities of P-glycoprotein substrate drugs. The present study aimed to explore the effect of nine naturally occurring ginsenosides and their intestinal bacterial metabolites on P-glycoprotein-mediated transport. The results showed that three ginsenoside metabolites (CK, Ppd, and Ppt) formed by intestinal bacteria significantly enhanced rhodamine 123 retention in Caco-2 cells, increased the absorptive permeability of rhodamine 123, and decreased the efflux ratio of digoxin in two absorption models, which were comparable to the effects of the known P-glycoprotein inhibitor verapamil. However, the prototype ginsenosides such as Rb1, Rb2, and Re showed no inhibitory effect on P-glycoprotein activity. In situ intestinal perfusion experiments also showed that CK, Ppd, and Ppt increased the absorption rate constant and permeability coefficient of rhodamine 123. Long-term treatment with CK, Ppd, and Ppt had no effect on P-glycoprotein mRNA expression in Caco-2 cells. In conclusion, CK, Ppd, and Ppt are potent P-glycoprotein inhibitors, indicating an unpredictable herb-drug interaction when ginsenosides are coadministered orally with P-glycoprotein substrate drugs.
关键词[WOS]: MEDIATED MULTIDRUG-RESISTANCE ;  HERB-DRUG INTERACTIONS ;  CACO-2 CELL MONOLAYER ;  COMPOUND K ;  20(S)-GINSENOSIDE RH2 ;  INTESTINAL-ABSORPTION ;  ORAL BIOAVAILABILITY ;  MCF-7/ADR CELLS ;  TUMOR-CELLS ;  RED GINSENG
语种: 英语
WOS记录号: WOS:000332395000007
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/144432
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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Dalian Med Univ, Dalian, Peoples R China

Recommended Citation:
Li, Na,Wang, Dandan,Ge, Guangbo,et al. Ginsenoside Metabolites Inhibit P-Glycoprotein In Vitro and In Situ Using Three Absorption Models[J]. PLANTA MEDICA,2014,80(4):290-296.
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