The Induction of CYP1A2, CYP2D6 and CYP3A4 by Six Trade Herbal Products in Cultured Primary Human Hepatocytes

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Abstract
Abstract: The aim of this study was to evaluate thein vitroinductive potential of six commonly used trade herbal products on CYP1A2, CYP2D6 and CYP3A4 metabolic activities. Herbal components were extracted from the trade products in a way that ensured a composition equal to that present in the original product. Primary human hepatocytes and specific CYP substrates were used. Classic inducers were used as positive controls and herbal extracts were added inin vivo‐relevant concentrations. Metabolites were determined by high performance liquid chromatography (HPLC). St. John's wort and common valerian were the strongest inducing herbs. In addition to induction of CYP3A4 by St. John's wort, common valerian andGinkgo bilobaincreased the activity of CYP3A4 and 2D6 and CYP1A2 and 2D6, respectively. A general inhibitory potential was observed for horse chestnut,Echinacea purpureaand common sage. St. John's wort inhibited CYP3A4 metabolism at the highest applied concentration. Horse chestnut might be a herb with high inhibition potentialsin vivoand should be explored further at lower concentrations. We show for the first time thatG. bilobamay exert opposite and biphasic effects on CYP1A2 and CYP2D6 metabolism. Induction of CYP1A2 and inhibition of CYP2D6 were found at low concentrations; the opposite was observed at high concentrations. CYP2D6 activity, regarded generally as non‐inducible, was increased by exposure to common valerian (linear to dose) andG. biloba (highest concentration). An allosteric activation is suggested. From the data obtained,G. biloba, common valerian and St. John's wort are suggested as candidates for clinically significant CYP interactionsin vivo.