Echinacea purpurea up-regulates CYP1A2, CYP3A4 and MDR1 gene expression by activation of pregnane X receptor pathway.
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.
Division of Clinical Pharmacology, Faculty of Medicine and Health Sciences, University of Stellenbosch , Cape Town , South Africa .
Charles
C
Awortwe
Vamshi K
VK
Manda
Cristina
C
Avonto
Shabana I
SI
Khan
Ikhlas A
IA
Khan
Larry A
LA
Walker
Patrick J
PJ
Bouic
Bernd
B
Rosenkranz
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D055162:Biocatalysis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D020900:Echinacea / Q000737:chemistry*; D017930:Genes, Reporter; D056945:Hep G2 Cells; D041743:Herb-Drug Interactions; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D000077297:Pregnane X Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism*; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D010936:Plant Extracts; D000077297:Pregnane X Receptor; D012333:RNA, Messenger; D011987:Receptors, Steroid; D008156:Luciferases; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A
Activation; E. purpurea; cytochrome P450 enzymes (CYPs); human liver carcinoma (HepG2); human pregnane xenobiotic receptor (hPXR)