Planta Med 2015; 81 - PG14
DOI: 10.1055/s-0035-1556245

Drug interaction potential of Mitragyna speciosa and its constituents through PXR modulation

SI Khan 1, 2, VK Manda 1, OR Dale 1, Z Ali 1, LA Walker 1, 2, IA Khan 1, 2
  • 1National Center for Natural Products Research
  • 2Department of Biomolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677

The leaves of Mitragyna speciosa (kratum), which are rich in alkaloids, are traditionally consumed for the stimulant and euphoric effects and as a substitute for opium. This study was conducted to predict the drug interaction potential of kratum with concomitantly used conventional drugs by determining the effects of its methanolic extract, an alkaloid enriched fraction and the isolated constituents (indole and oxindole alkaloids) on pregnane X receptor (PXR)-mediated expression of drug metabolizing enzymes (CYPs) and transporters (P-gp). A significant activation of PXR was observed with the extract and the alkaloid fraction with EC50 of 18 and 8 µg/mL, respectively. Several of the isolated constituents increased PXR activity with EC50 values in the range of 2 – 6µM. A significant increase in the expression of mRNA for CYP1A2 and P-gp was observed by the total extract, alkaloid enriched fraction and eight of the isolated constituents while CYP3A4 mRNA was increased only by four constituents. These results indicate that chronic use or high consumption of Mitragyna speciosa may affect the pharmacokinetics and pharmacodynamics of co-administered drugs which are substrates of CYPs and P-gp by altering their metabolism and transport. Further in vivo studies are warranted.