2. Academic Validation
  3. The potential role of human multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 2 (MRP2) in the transport of Huperzine A in vitro

The potential role of human multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 2 (MRP2) in the transport of Huperzine A in vitro

  • Xenobiotica. 2020 Mar;50(3):354-362. doi: 10.1080/00498254.2019.1623935.
Ziyan Fei 1 2,  Mengyun Hu 1 2,  Larry Baum 3 4,  Patrick Kwan 5 6,  Tao Hong 7,  Chunbo Zhang 1 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Nanchang University, Nanchang, PR China.
  • 2 Provincial Key Laboratory for Drug Targeting and Drug Screening Research, Nanchang, PR China.
  • 3 The State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Pokfulam, Hong Kong, PR China.
  • 4 Centre for Genomic Sciences, University of Hong Kong, Pokfulam, Hong Kong, PR China.
  • 5 Department of Neuroscience, Alfred Hospital, Monash University, Melbourne, Australia.
  • 6 Departments of Medicine and Neurology, Royal Melbourne Hospital, The University of Melbourne, Melbourne, Australia.
  • 7 Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, PR China.
PMID: 31132291 DOI: 10.1080/00498254.2019.1623935
Abstract

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 µg/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.

Keywords

Hup-A; P-glycoprotein; cell monolayer; drug transporter; drug-resistant epilepsy.

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