Evaluation Of The Influence Of Selected Herbal Extracts On The Activity Of P-Glycoprotein And Pregnane X Receptor Activation

Pregnane X receptor (PXR) regulates the expression of drug metabolizing enzymes (DME). Its activation by herbal products is an indicator for increased DME expression which can increase the metabolic rate of co-administered drugs. P-glycoprotein (P-gp) is a major drug transporter in the gastro-intestinal tract whose inhibition can affect the uptake and transport of drugs. We examined the effects of seven selected herbal extracts on P-gp activity and PXR activation. The inhibition of P-gp was conducted in MDCK-II and hMDR1-MDCK-II cells in terms of calcein-AM uptake and modulation of PXR activity was conducted in HepG2 cells by luciferase reporter gene assay [1]. Extracts of Phyllanthus amarus, Momordica charantia, Tithonia diversifolia and Annona aff. muricata exhibited significant P-gp inhibition with IC₅₀ values (µg/mL) of 17 ± 1.4, 16 ± 0.3, 26 ± 1.1, and 24 ± 0.9, respectively while extracts of Argemone mexicana, Momordica charantia, Phyllanthus amarus and Tithonia diversifolia showed > 2 fold induction in PXR activity. The results suggest that the selected herbal extracts may exert herb-drug interactions through the inhibition of P-gp and activation of PXR.

Acknowledgements: Study supported by USAID grant for Africa-U.S. Higher Education Partnership program, USAID/HED Grant No HED 153 – 6200-BFA-15 – 01

Reference: Manda VK, Dale OR, et al. 2014. Front Pharmacol. 5: 178