The inhibition of human cytochrome P450 by ethanol extracts of North American botanicals

Abstract

High-throughput enzyme inhibition screening assays were used to quantify the effect of ethanol extracts of 2 accessions of 10 North American (NA) botanicals against the activity of the human cytochrome P450s: CYP3A4, CYP19, and CYP2C19. In addition, phytochemical biomarkers within each extract were identified and quantified using HPLC-MS or GC. Extracts containing uncharacterized phytochemicals were identified taxonomically. The overall objective was to describe the relationship between types and quantities of phytochemicals in ethanol extracts and their ability to inhibit CYP activity. The top three inhibitors of CYP3A4 were Gaultheria procumbens L. leaf > Rhodiola rosea L. root > Arctostaphylos uva-ursi L. Spreng leaf; of CYP19 were R. rosea root > Rhododendron groenlandicum (Oeder) Kron & Judd leaf > A. uva-ursi leaf; and of CYP2C19 were Achillea millefolium L. leaf and flower > Vaccinium sp. L. leaf > Polygala senega L. root. Equisetum arvense L. leaf, Arctium lappa L. root, and P. senega root had the least effect on CYP3A4 and CYP19 activity. These results suggest that North American botanicals have the potential to inhibit the metabolism of drug-specific CYPs in vivo , causing a direct shift in the availability of drugs and their pharmacokinetics in the body. Furthermore, the concentration of certain phytochemical markers varied significantly between accessions (i.e., rosarin and essential oils), suggesting that the extent of metabolic inhibition is directly dependent upon the concentration of bioactive constituents in an extract. © 2006 Taylor & Francis Group, LLC.