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Planta Med 2014; 80(04): 290-296
DOI: 10.1055/s-0033-1360334
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Ginsenoside Metabolites Inhibit P-Glycoprotein In Vitro and In Situ Using Three Absorption Models

Na Li
1   Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
2   University of Chinese Academy of Sciences, Beijing, China
,
Dandan Wang
1   Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
2   University of Chinese Academy of Sciences, Beijing, China
,
Guangbo Ge
1   Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
,
Xiuli Wang
3   Dalian Medical University, Dalian, China
,
Yong Liu
1   Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
,
Ling Yang
1   Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
› Author Affiliations
Further Information

Publication History

received 15 August 2013
revised 05 December 2013

accepted 05 January 2014

Publication Date:
03 February 2014 (online)

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Abstract

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.

Key words

ginseng - ginsenoside - intestinal metabolism - P-glycoprotein - inhibitor
 

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