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  4. An in vitro evaluation of cytochrome P450 inhibition and p-glycoprotein interaction with goldenseal, ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents

An in vitro evaluation of cytochrome P450 inhibition and p-glycoprotein interaction with goldenseal, ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents

Etheridge, A., Black, S., Patel, P., So, J., & Mathews, J. (2007). An in vitro evaluation of cytochrome P450 inhibition and p-glycoprotein interaction with goldenseal, ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constituents. Planta Medica, 73(8), 731-741. https://doi.org/10.1055/s-2007-981550

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Abstract

Drug-herb interactions can result from the modulation of the activities of cytochrome P450 (P450) and/or drug transporters. The effect of extracts and individual constituents of goldenseal, Ginkgo biloba (and its hydrolyzate), grape seed, milk thistle, and ginseng on the activities of cytochrome P450 enzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4 in human liver microsomes were determined using enzyme-selective probe substrates, and their effect on human P-glycoprotein (Pgp) was determined using a baculovirus expression system by measuring the verapamil-stimulated, vanadate-sensitive ATPase activity. Extracts were analyzed by HPLC to standardize their concentration(s) of constituents associated with the pharmacological activity, and to allow comparison of their effects on P450 and Pgp with literature values. Many of the extracts/constituents exerted ? 50 % inhibition of P450 activity. These include those from goldenseal (normalized to alkaloid content) inhibiting CYP2C8, CYP2D6, and CYP3A4 at 20 ?M, ginkgo inhibiting CYP2C8 at 10 ?M, grape seed inhibiting CYP2C9 and CYP3A4 at 10 ?M, milk thistle inhibiting CYP2C8 at 10 ?M, and ginsenosides F1 and Rh1 (but not ginseng extract) inhibiting CYP3A4 at 10 ?M. Goldenseal extracts/constituents (20 ?M, particularly hydrastine) and ginsenoside Rh1 stimulated ATPase at about half of the activity of the model substrate, verapamil (20 ?M). The data suggest that the clearance of a variety of drugs may be diminished by concomitant use of these herbs via inhibition of P450 enzymes, but less so by Pgp-mediated effects.

10.1055/s-2007-981550

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