An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures

• Published in: Phytomedicine (Stuttgart) 2000-07, Vol.7 (4), p.273-282
• Main Authors: Budzinski, J.W., Foster, B.C., Vandenhoek, S., Arnason, J.T.
• Format: Article
• Language: English
• Subjects: commercial herbal extracts and tinctures; CYP3A4; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - drug effects; cytochrome P450; Dose-Response Relationship, Drug; Drug Interactions; herbal-drug interactions; Humans; inhibition; Mixed Function Oxygenases - antagonists & inhibitors; Mixed Function Oxygenases - drug effects; Plant Extracts - pharmacology; Plants, Medicinal; potential risk
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/S0944-7113(00)80044-6

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC 50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC 50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC 50 values ranging from 1%–2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC 50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole. Utilizing high-throughput screening methodologies for assessing CYP3 A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.