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Molecules 2016, 21(12), 1606;

Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport

Key Laboratory of Modern Preparation of TCM, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
Author to whom correspondence should be addressed.
Academic Editor: Maria Emília de Sousa
Received: 20 September 2016 / Revised: 16 November 2016 / Accepted: 16 November 2016 / Published: 24 November 2016
(This article belongs to the Special Issue Can Membrane Transporters Contribute to Drug Discovery?)
Full-Text   |   PDF [2006 KB, uploaded 24 November 2016]   |  


P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known. The present study investigated the mechanism by which imperatorin promotes P-gp-mediated drug transport. We used molecular docking to predict the binding force between imperatorin and P-gp and the effect of imperatorin on P-gp activity. P-gp efflux activity and P-gp ATPase activity were measured using a rhodamine 123 (Rh-123) accumulation assay and a Pgp-Glo™ assay; respectively. The fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess cellular membrane fluidity in MDCK-MDR1 cells. Western blotting was used to analyze the effect of imperatorin on P-gp expression; and P-gp mRNA levels were assessed by qRT-PCR. Molecular docking results demonstrated that the binding force between imperatorin and P-gp was much weaker than the force between P-gp and verapamil (a P-gp substrate). Imperatorin activated P-gp ATPase activity; which had a role in the inhibition of P-gp activity. Imperatorin promoted Rh-123 accumulation in MDCK-MDR1 cells and decreased cellular membrane fluidity. Western blotting demonstrated that imperatorin inhibited P-gp expression; and qRT-PCR revealed that imperatorin down-regulated P-gp (MDR1) gene expression. Imperatorin decreased P-gp-mediated drug efflux by inhibiting P-gp activity and the expression of P-gp mRNA and protein. Our results suggest that imperatorin could down-regulate P-gp expression to overcome multidrug resistance in tumors. View Full-Text
Keywords: imperatorin; P-glycoprotein (P-gp); transmembrane transport; mechanism imperatorin; P-glycoprotein (P-gp); transmembrane transport; mechanism

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Liao, Z.-G.; Tang, T.; Guan, X.-J.; Dong, W.; Zhang, J.; Zhao, G.-W.; Yang, M.; Liang, X.-L. Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport. Molecules 2016, 21, 1606.

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