ORIGINAL ARTICLESSt. John's wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in basic cellular pathwaysKrusekopf, Solveigh; Roots, IvarAuthor Information Institute of Clinical Pharmacology, Charité Campus Mitte, Charité University Medical Center, Humboldt University of Berlin, Berlin, Germany Correspondence and requests for reprints to Solveigh Krusekopf, Institut für Klinische Pharmakologie, Charité Campus Mitte, Schumannstr. 20/21, D-10117 Berlin, Germany. Tel: +49 30 94 06 28 45; fax: +49 30 450 52 59 32; e-mail: [email protected] Received 1 April 2005 Accepted 18 June 2005 Pharmacogenetics and Genomics: November 2005 - Volume 15 - Issue 11 - p 817-829 doi: 10.1097/01.fpc.0000175597.60066.3d Buy Metrics Abstract Objectives and methods The effects of St. John's wort and hyperforin on gene expression were analysed in HepG2 cells by Affymetrix microarray hybridization and real time reverse transcription–PCR. Results Both compounds increased mRNAs of the drug metabolizing enzymes CYP3A4, CYP1A1, CYP1A2 and the flavin containing monooxygenase FMO5, and of the multidrug resistance protein MRP2. CYP4F2 and the reduced nicotinamide adenine dinucleotide dehydrogenase NQO1 were downregulated. Expression of genes mediating cholesterol biosynthesis was decreased, while facilitated glucose transporters and glycolysis genes were induced, indicating increased glucose metabolism. Changes of a considerable number of additional transcripts corresponded to reports on gene regulation by hypoxia. Endoplasmic reticulum stress-regulated genes involved in unfolded protein response and in protection of cells from apoptosis were downregulated. Other calcium binding proteins were affected by both treatments, suggesting an increase in intracellular calcium. Conclusions St. John's wort and hyperforin concordantly affected expression of genes not only mediating metabolism and transport of exogenous and endogenous compounds, but also involved in energy metabolism, intracellular calcium regulation, cell proliferation and apoptosis. © 2005 Lippincott Williams & Wilkins, Inc.