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高等学校化学研究 ›› 2014, Vol. 30 ›› Issue (5): 731-737.doi: 10.1007/s40242-014-4066-2

• Articles • 上一篇    下一篇

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. 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
  • 收稿日期:2014-03-03 修回日期:2014-04-25 出版日期:2014-10-01 发布日期:2014-05-12
  • 通讯作者: LIU Zhongying E-mail:liuzy@jlu.edu.cn
  • 基金资助:

    Supported by the Natural Science Foundation of Jilin Province, China(No.201115045) and the National Natural Science Foundation of China(Nos.81173507, 81274046).

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. 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).

摘要:

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.

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

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)