Trade herbal products and induction of CYP2C19 and CYP2E1 in cultured human hepatocytes.
The aim of this study was to evaluate in vitro the dose-dependent induction potential of six commonly used trade herbal products on CYP2C19 and CYP2E1 metabolic activities in cultured human hepatocytes. S-mephenytoin and chlorzoxazone were used as specific CYP substrates, respectively, and rifampicin was used as a positive induction control for both enzymes. The hepatocytes were exposed to herbal extracts in increasing and biological relevant concentrations for 72 hrs and CYP substrate metabolites were quantified by validated HPLC methodologies. The major findings were that St John's wort was the most potent CYP-modulating herb, showing a dose-dependent induction/inhibition of both CYP2C19 and CYP2E1, with induction at low dosages and inhibition at higher. Ginkgo biloba showed an induction/inhibition profile towards CYP2C19 which was similar but weaker than that observed for St John's wort. If cooperative mechanisms are involved is still an open question. Common sage induced CYP2C19 in a log-linear dose-dependent manner with increasing concentrations. Common valerian was a weak inducer of CYP2C19, while horse chestnut and cone flower were characterized as non-inducers of CYP2C19. Only St John's wort showed an inductive effect towards CYP2E1. In addition to St John's wort, Gingko biloba and common sage should be considered as possible candidates for clinically relevant drug-herb interactions with selected CYP2C19 substrates.
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. bent.h.hellum@ntnu.no
Bent H
BH
Hellum
Zhuohan
Z
Hu
Odd Georg
OG
Nilsen
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002478:Cells, Cultured; D065731:Cytochrome P-450 CYP2C19; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology; D041743:Herb-Drug Interactions; D006801:Humans; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*
D010936:Plant Extracts; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19