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In vitro CYP3A4 Metabolism: Inhibition by Echinacea purpurea and Choice of Substrate for the Evaluation of Herbal Inhibition
Author(s) -
Hansen Torstein Schrøder,
Nilsen Odd Georg
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00307.x
Subject(s) - cyp3a4 , ketoconazole , echinacea (animal) , substrate (aquarium) , in vitro , metabolism , chemistry , pharmacology , cytochrome p450 , biology , biochemistry , traditional medicine , medicine , antifungal , ecology , microbiology and biotechnology
The in vitro CYP3A4 inhibition profiles of Echinacea purpurea , St. John's wort and ketoconazole were evaluated by three different substrates: 7‐benzyloxy‐trifluoromethylcoumarin (BFC), 7‐benzyloxyquinoline (BQ) and testosterone. St. John's wort and ketoconazole produced similar inhibition profiles regardless of substrate. For E. purpurea , testosterone metabolism showed a much lower CYP3A4 inhibition (IC 50 5394 µg/ml) compared to the fluorescent substrates BFC and BQ (IC 50 354 and 452 mg/ml, respectively). It is suggested that the substrate/assay‐dependent effects may arise from a complex nature of E. purpurea constituents, involving different CYP3A4 substrate binding sites. The choice of substrate might thus be essential for evaluation of the inhibition of CYP3A4 metabolism for some herbs. A weak inhibition potential of E. purpurea towards CYP3A4‐mediated metabolism in vitro was confirmed by the use of three different substrates.