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Title: Interactions of Echinacea liquid preparations and selected constituents with the cytochrome P450 enzyme system
Author: Modarai, Maryam
ISNI:       0000 0004 2670 7258
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2008
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Despite the increasing use and popularity of Echinacea in the treatment of upper respiratory tract infections, little is known about its interactions with conventional medicines. Recent legislation changes have made it necessary to investigate potential interactions between herbal medicinal products and the CYP P450 system. To address this knowledge gap we measured the CYP P450 inhibition of Echinaforce® and nine more commercial Echinacea liquid preparations (ELP), along with selected constituents, with a modified fluorogenic assay. We demonstrated that all Echinacea preparations and all alkylamides assessed, directly inhibited CYP3A4. In addition Echinaforce® weakly inhibited CYP2D6, CYP2C19 and CYP1A2, while alkylamides 1 and 2 inhibited 2D6 and 2C19, but not 1A2. We observed no inhibition with caffeic acid but the results for three caffeic acid derivatives were inconclusive. Separation of six ELP (including Echinaforce®) into ethanol and water soluble components showed that most of the inhibitory activity resided in the ethanol fraction. Multivariate data analysis of 1H-NMR spectra of the ethanol fractions identified peaks linked with inhibitory activity. SPE fractionation of the ethanol fraction of Echinaforce® produced three active fractions. These were further analyzed by LC-MS (positive ion mode), revealing two major components, with molecular ion [M-H]+ masses of 282 and 248. Tandem MS and accurate mass analysis revealed that the 248 ion is in fact alkylamide 1, while ion 282 is most likely an unknown compound with molecular formula C18H36NO+ for which we have deduced a tentative structure. To assay for CYP3A4 induction we exposed HepG2 cells to relevant concentrations of Echinaforce® and alkylamides 1 and 2, but no significant changes in mRNA steady state levels were seen. Overall our results (in agreement with the available pharmacovigilance data) suggested that ELP are unlikely to cause clinically observable interactions with prescription medicines via the CYP P450 system, but that the observed effects vary widely in accordance with the products' chemical composition.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available