Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein

doi:10.1007/s40242-014-4066-2

Chemical Research in Chinese Universities ›› 2014, Vol. 30 ›› Issue (5): 731-737.doi: 10.1007/s40242-014-4066-2

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Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein

MA Jingwei¹, KAN Hong¹, MA Yinghui¹, MEN Lihui¹, PI Zifeng², LIU Zhiqiang², LIU Zhongying¹

1. College of Pharmacy, Jilin University, Changchun 130021, P. R. China;
2. Changchun Center of Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China

Received:2014-03-03 Revised:2014-04-25 Online:2014-10-01 Published:2014-05-12
Contact: LIU Zhongying E-mail:liuzy@jlu.edu.cn
Supported by:
Supported by the Natural Science Foundation of Jilin Province, China(No.201115045) and the National Natural Science Foundation of China(Nos.81173507, 81274046).

Abstract

Abstract:

Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry(UPLC-ESI-MS) was used to investigate the potential interaction between selected ingredients of Aconitum and fritillary. The efflux ratios of 14-benzoylmesaconine(BM), 14-benzoylaconine(BC), 14-benzoylhypaconine(BH), mesaconitine(MA), aconitine(AC) and hypaconitine(HA) was 11.16, 12.53, 11.69, 12.8, 11.03 and 6.15, respectively, and the secretion of them was inhibited by Verapamil, which means they are the substrates of permeability-glycoprotein(P-gp). The transport of Aconitum alkaloids extract through a Caco-2 cell monolayer was determined in the absence and presence of fritillary extract. And the fritillary extract increased the absorption of Aconitum alkaloids. Peimine(PE) and peiminine(PEN) in fritillary increased the absorption of pure Aconitum alkaloids. The transport of digoxin was respectively enhanced by PE and PEN, which means they are the inhibitors of P-gp. PEN showed more effective inhibition than PE at the same concentration. The in vitro data suggest that the compounds such as fritillary present in alkaloids were able to inhibit the P-gp activity and lead modifying the transport of alkaloids.

Key words: Aconitum alkaloid, Fritillary, Caco-2 cell, Permeability-glycoprotein(P-gp), Ultra performance liquid chromatographic-electrospray ionization-mass spectrometry(UPLC-ESI-MS)

MA Jingwei, KAN Hong, MA Yinghui, MEN Lihui, PI Zifeng, LIU Zhiqiang, LIU Zhongying. Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein[J]. Chemical Research in Chinese Universities, 2014, 30(5): 731-737.

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Qualitative and Quantitative Analysis of Drug Interactions: Fritillary Mediating the Transport of Alkaloids in Caco-2 Cells by P-Glycoprotein

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