Journal
XENOBIOTICA
Volume 50, Issue 3, Pages 354-362Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/00498254.2019.1623935
Keywords
P-glycoprotein; Hup-A; drug-resistant epilepsy; drug transporter; cell monolayer
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Funding
- National Natural Science Foundation of China [NSFC-31771400, NSFC-81728006, NSFC-81501129, NSFC-81860662]
- Natural Science Foundation of Jiangxi Province [20161BAB215200, 20171ACB21001, 20171BCB23029]
- Science and Technology Project of Jiangxi Provincial Education Department [150111]
- Science and Technology Project of Health and Family Planning Commission of Jiangxi Provence [20175534]
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1. More than 30% of epilepsy patients suffer pharmacoresistance. Transport of antileptic drugs by P-glycoprotein (P-gp) and MRP2 plays an important role in drug-resistant epilepsy. Huperzine A (Hup-A) is a natural compound, which might have potential in treating neurological disorders including epilepsy and Alzheimer's disease. In this study, we investigated whether human P-gp and MRP2 transport Hup-A. 2. LLC-PK1 and MDCKII cells transfected with human P-gp or MRP2 were used to establish concentration equilibrium transport assays (CETAs) and determine the transport profile of Hup-A. The expression of P-gp and MRP2 was detected by qPCR and western blotting. The transport function of P-gp and MRP2 was measured by Rho123 and CDFDA cell uptake assay. 3. In CETAs, Hup-A at concentrations of 10 ng/mL or 2 mu g/mL was transported by MDR1 and MRP2 from basolateral to apical sides of the cell monolayers. P-gp and MRP2 inhibitors completely blocked the efflux of Hup-A. There was no efflux of Hup-A in LLC-PK1 or MDCKII wild-type (WT) cells. 4. We demonstrate that Hup-A is a substrate of P-gp and MRP2. These results imply the efflux of Hup-A across the blood-brain barrier (BBB) in vivo, suggesting potential drug resistance of Hup-A.
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