Abstract
An important safety concern with herbal medicinal products (HMP) is interactions with conventional medicines, particularly ones mediated by the Cytochrome P450 enzyme system (CYP). Previously, we established that
Echinacea
and its immunomodulatory alkylamides [1] can weakly inhibit the activity of the main drug metabolising CYP isoforms [2]. However, the ability of
Echinacea
to alter CYP expression levels is not well characterized. In this study we investigate whether exposure of HepG2 cells to a commercial
Echinacea
extract (Echinaforce
®
) and four alkylamides (dodeca-2
E
,4
E
,8
Z
,10
E/Z-
tetranoic acid isobutylamide (
1
), dodeca-2
E
,4
E-
dieonoic acid isobutylamide (
2
), undec-2
E/Z
-ene-8,10-diyonic acid isobutylamides (
3
) and dodec-2-ene-8,10-diyonic acid isobutylamide (
4
)) can promote the transcription of CYP3A4 (the most important drug metabolizing CYP).
HepG2 cells were treated for 96 hours with clinically relevant concentrations of either Echinaforce
®
(22µg/ml or 11.6µg/ml or 1.16µg/ml) or the alkylamides (1.62 nM or 44 nM). Real-time RT-PCR analysis demonstrated that there were no statistically significant changes in the steady state mRNA levels of CYP3A4 compared to the vehicle control (medium with 0.1% ethanol). In contrast, treatment with 50µM rifampicin resulted in a 3.8-fold upregulation of the steady state mRNA level of CYP3A4. Observations of β-actin upregulation by Echinaforce
®
in human monocytes/macrophages [1] do not appear to be relevant to HepG2 cells. Using GAPDH as a reference gene we found that β-actin was not upregulated by Echinaforce
®
or its alkylamides in HepG2 cells. Our data suggest
Echinacea
is unlikely to affect the transcription of CYP3A4, at concentrations previously shown to induce mild CYP 3A4 inhibition.
Acknowledgements: Bioforce and the Mapplethorpe Trust Fund, University of London, for funding this project.
References:
[1] Gertsch, J. et al. (2004) FEBS letters 577:563–569.
[2] Modarai, M. et al. (2007)J. Pharm. Pharmacol. 59:567–573.