Skip to Content
Merck
  • PXR mediated induction of CYP3A4, CYP1A2, and P-gp by Mitragyna speciosa and its alkaloids.

PXR mediated induction of CYP3A4, CYP1A2, and P-gp by Mitragyna speciosa and its alkaloids.

Phytotherapy research : PTR (2017-10-27)
Vamshi K Manda, Bharathi Avula, Olivia R Dale, Zulfiqar Ali, Ikhlas A Khan, Larry A Walker, Shabana I Khan
ABSTRACT

Kratom (Mitragyna speciosa), a native herb of Southeast Asia, is widely known for its psychoactive properties. Recent increase in the use of kratom as a recreational drug has increased the risk of its interaction with conventional drugs if taken concomitantly. A few reports are available related to the effects of kratom on the activity of cytochrome P450 enzymes (CYPs), but there are no reports of its effects on pregnane X receptor (PXR), a transcription factor that regulates the expression of CYPs and P-glycoprotein (P-gp). This study was carried out to evaluate the effects of a methanolic extract of kratom leaves, an alkaloid rich fraction and its 5 indole and 4 oxindole alkaloids on PXR activation and the resulting changes in the mRNA expression of PXR target genes (CYP3A4, CYP1A2, and P-gp). A significant activation of PXR was observed by the extract (3-fold), alkaloidal fraction (4-fold) and all 9 alkaloids (4- to 6-fold) that was associated with an increased mRNA expression which resulted into an increase in the activity of CYP3A4, CYP1A2, and P-gp. These results indicate that high consumption of Mitragyna speciosa extract along with the conventional drugs may lead to potential herb-drug interactions due to its effects on PXR.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
7-Benzyloxy-4-trifluoromethylcoumarin, ≥99% (HPLC), solid