Abstract Title:

Safety of Herbal Medicinal Products: Echinacea and Selected Alkylamides do not Induce CYP3A4 mRNA Expression.

Abstract Source:

Evid Based Complement Alternat Med. 2009 Nov 11. Epub 2009 Nov 11. PMID: 19906827

Abstract Author(s):

Maryam Modarai, Elisabete Silva, Andy Suter, Michael Heinrich, Andreas Kortenkamp

Article Affiliation:

Centre for Toxicology, The School of Pharmacy, University of London, 29/39 Brunswick Square, London, WC1N 1AX, UK. Tel/ andreas.kortenkamp@pharmacy.ac.uk.

Abstract:

A major safety concern with the use of herbal medicinal products (HMP) is their interactions with conventional medicines, which are often mediated via the cytochrome P450 (CYP) system. Echinacea is a widely used over-the-counter HMP, with proven immunomodulatory properties. Its increasing use makes research into its safety an urgent concern. Previously, we showed that Echinacea extracts and its alkylamides (thought to be important for Echinacea's immunomodulatory activity) mildly inhibit the enzymatic activity of the main drug metabolising CYP isoforms, but to this date, there is insufficient work on its ability to alter CYP expression levels. We now report for the first time the effect of a commercial Echinacea extract (Echinaforce(R)) and four Echinacea alkylamides on the transcription of the major drug metabolizing enzyme CYP3A4. HepG2 cells were exposed for 96 h to clinically relevant concentrations of Echinaforce (22, 11.6 and 1.16 microg ml(-1)) or the alkylamides (1.62 and 44 nM). CYP3A4 mRNA levels were quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Neither Echinaforce(R) nor the alkylamides produced any significant changes in the steady-state CYP3A4 mRNA levels, under these conditions. In contrast, treatment with 50 microM rifampicin resulted in a 3.8-fold up-regulation over the vehicle control. We conclude that Echinaforce(R) is unlikely to affect CYP3A4 transcriptional levels, even at concentrations which can inhibit the enzymatic activity of CYP3A4. Overall, our data provides further evidence for the lack of interactions between Echinacea and conventional drugs.

Study Type : In Vitro Study
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