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St. John's wort and its constituent hyperforin concordantly regulate expression of genes encoding enzymes involved in
Solveigh Krusekopf1, Ivar Roots
1Institute of Clinical Pharmacology, Charité Campus Mitte, Charité University Medical Center, Humboldt University of Berlin, Berlin, Germany. Solveigh.Krusekopf@charite.de
Pharmacogenetics and Genomics
|October 13, 2005
Summary
St. John's wort and hyperforin alter gene expression in liver cells. These compounds impact drug metabolism, glucose processing, and cellular stress responses, affecting key biological pathways.
Area of Science:
- Pharmacogenomics
- Molecular Biology
- Hepatology
Background:
- St. John's wort is a popular herbal remedy with known drug interactions.
- Hyperforin is a key active component of St. John's wort.
- Understanding their effects on cellular machinery is crucial for safety and efficacy.
Purpose of the Study:
- To investigate the impact of St. John's wort and hyperforin on gene expression profiles in human liver cells (HepG2).
- To identify specific genes and pathways regulated by these compounds.
Main Methods:
- Affymetrix microarray hybridization was used for global gene expression analysis.
- Real-time reverse transcription-PCR (RT-PCR) validated key gene expression changes.
Main Results:
- Upregulation of drug-metabolizing enzymes (CYP3A4, CYP1A1, CYP1A2), FMO5, and MRP2.
- Downregulation of CYP4F2, NQO1, cholesterol biosynthesis genes, and endoplasmic reticulum stress response genes.
- Induction of glucose transporters and glycolysis genes, suggesting altered glucose metabolism.
- Evidence of increased intracellular calcium and hypoxia-related gene expression changes.
Conclusions:
- St. John's wort and hyperforin exert concordant effects on genes involved in xenobiotic/endobiotic metabolism and transport.
- These compounds significantly influence energy metabolism, intracellular calcium homeostasis, and cellular processes like proliferation and apoptosis.