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

• Published in: Xenobiotica 2015-03, Vol.45 (3), p.218-229
• Main Authors: Awortwe, Charles, Manda, Vamshi K., Avonto, Cristina, Khan, Shabana I., Khan, Ikhlas A., Walker, Larry A., Bouic, Patrick J., Rosenkranz, Bernd
• Format: Article
• Language: English
• Subjects: Activation; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family 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; cytochrome P450 enzymes (CYPs); E. purpurea; Echinacea - chemistry; Genes, Reporter; Hep G2 Cells; Herb-Drug Interactions; human liver carcinoma (HepG2); human pregnane xenobiotic receptor (hPXR); Humans; Luciferases - metabolism; Plant Extracts - pharmacology; Receptors, Steroid - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Time Factors; Transcriptional Activation - drug effects; Transcriptional Activation - genetics; Up-Regulation - drug effects
• ISSN: 0049-8254; 1366-5928
• DOI: 10.3109/00498254.2014.973930

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.