Phytochemical variation in Canadian Hydrastis canadensis L (goldenseal) and the in vitro inhibition of human cytochrome P450-mediated drug metabolism by H canadensis and other botanicals

Abstract

To promote recovery and crop potential of Hydrastis canadensis---a botanical threatened in Canada---wild populations were phytochemically surveyed. Berberine, hydrastine and canadine were characterized in root-rhizome, stem-leaf, and berry pulp. Comparisons with cultivated material showed no difference in alkaloid content, thus the medicinal value of cultivated material is not likely increased with addition of wild plants. Quantitative analyses suggested genetic diversity among wild populations. Regression analyses indicated a minor relationship between latitude and alkaloid yield. Because H. canadensis and other botanicals may cause adverse botanical-drug interactions, 22 botanicals were assayed for cytochrome P450 (CYP) 2C19, CYP3A4 and CYP19 inhibition. Eight botanicals inhibited CYP2C19 by ≥ 57%, 17 inhibited CYP3A4 by ≥ 40% and CYP19 by ≥ 50%, of which Arctostaphylos uva-ursi, H canadensis, Oenothera biennis, Rhodiola rosea and Sanguinaria canadensis were most potent. Regression analyses indicated berberine concentration was a significant factor in CYP3A4 and CYP19 inhibition.