Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway

Xenobiotica. 2015 Mar;45(3):218-29. doi: 10.3109/00498254.2014.973930. Epub 2014 Nov 7.

Abstract

1.This study investigated the mechanism underlying Echinacea-mediated induction of CYP1A2, CYP3A4 and MDR1 in terms of human pregnane X receptor (PXR) activation. 2.Crude extracts and fractions of Echinacea purpurea were tested for PXR activation in HepG2 cells by a reporter gene assay. Quantitative real-time PCR was carried out to determine their effects on CYP1A2 and CYP3A4 mRNA expressions. Capsules and fractions were risk ranked as high, intermediate and remote risk of drug-metabolizing enzymes induction based on EC50 values determined for respective CYPs. 3. Fractions F1, F2 and capsule (2660) strongly activated PXR with 5-, 4- and 3.5-fold increase in activity, respectively. Echinacea preparations potentiated up-regulation of CYP1A2, CYP3A4 and MDR1 via PXR activation. 4.Thus E. purpurea preparations cause herb-drug interaction by up-regulating CYP1A2, CYP3A4 and P-gp via PXR activation.

Keywords: Activation; E. purpurea; cytochrome P450 enzymes (CYPs); human liver carcinoma (HepG2); human pregnane xenobiotic receptor (hPXR).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Biocatalysis / drug effects
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cytochrome P-450 CYP1A2 / genetics*
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Echinacea / chemistry*
  • Genes, Reporter
  • Hep G2 Cells
  • Herb-Drug Interactions
  • Humans
  • Luciferases / metabolism
  • Plant Extracts / pharmacology*
  • Pregnane X Receptor
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Steroid / metabolism*
  • Time Factors
  • Transcriptional Activation / drug effects
  • Transcriptional Activation / genetics
  • Up-Regulation / drug effects*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Plant Extracts
  • Pregnane X Receptor
  • RNA, Messenger
  • Receptors, Steroid
  • Luciferases
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 CYP3A