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Molecules 2017, 22(12), 2049; doi:10.3390/molecules22122049

Modulation of Cytochrome P450, P-glycoprotein and Pregnane X Receptor by Selected Antimalarial Herbs—Implication for Herb-Drug Interaction

1
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, NC 27506, USA
2
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
3
Department of Environmental Resources Engineering, State University of New York College of Environmental Science and Forestry, Syracuse, NY 13210, USA
4
Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
*
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Accepted: 20 November 2017 / Published: 23 November 2017
(This article belongs to the Collection Herbal Medicine Research)
View Full-Text   |   Download PDF [1946 KB, uploaded 23 November 2017]   |  

Abstract

Seven medicinal plants popularly used for treating malaria in West Africa were selected to assess herb-drug interaction potential through a series of in vitro methods. Fluorescent cytochrome P450 (CYP) assays were conducted using the recombinant CYP enzymes for CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 to assess the effect of the methanolic extracts on the metabolic activity of CYPs. Secondly, the inhibitory effect of the extracts was evaluated on P-glycoproteins (P-gp) using calcein-AM, a fluorescent substrate, in MDCK-II and hMDR1-MDCK-II cells. The inhibition of P-gp activity was determined as a reflection of increase in calcein-AM uptake. Additionally, the enzyme induction potential of the extracts was assessed through the modulation of PXR activity in HepG2 cells transiently transfected with pSG5-PXR and PCR5 plasmid DNA. Significant inhibition of CYP activity (IC50 < 10 µg/mL) was observed with the following herbs: A. muricata [CYP2C9, 3A4 and CYP2D6]; M. indica [CYP2C9]; M. charantia [CYP2C9 and CYP2C19]; P. amarus [CYP2C19, CYP2C9 and CYP3A4]; T. diversifolia [CYP2C19 and CYP3A4]. Extracts of four herbs (P. amarus, M. charantia, T. diversifolia and A. muricata) exhibited significant inhibition of P-gp with IC50 values (µg/mL) of 17 ± 1, 16 ± 0.4, 26 ± 1, and 24 ± 1, respectively. In addition, four herbs (A. mexicana, M. charantia, P. amarus and T. diversifolia) showed a >two-fold increase in induction in PXR activity. These findings suggest that these herbs may be capable of eliciting herb-drug interactions if consumed in high quantities with concomitant use of conventional therapies. View Full-Text
Keywords: cytochrome P450; drug metabolism; enzyme induction; herb-drug interaction; herbal medicine; malaria; P-glycoprotein; pregnane-X factor cytochrome P450; drug metabolism; enzyme induction; herb-drug interaction; herbal medicine; malaria; P-glycoprotein; pregnane-X factor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Fasinu, P.S.; Manda, V.K.; Dale, O.R.; Egiebor, N.O.; Walker, L.A.; Khan, S.I. Modulation of Cytochrome P450, P-glycoprotein and Pregnane X Receptor by Selected Antimalarial Herbs—Implication for Herb-Drug Interaction. Molecules 2017, 22, 2049.

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