St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor
Why is this work in the frame?
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No Canadian affiliation. An affiliation-only frame — the usual design — would never have seen this work. It is one of the works that make the case for inverting the frame.
Abstract
St. John's wort (Hypericum perforatum) is an herbal remedy used widely for the treatment of depression. Recent clinical studies demonstrate that hypericum extracts increase the metabolism of various drugs, including combined oral contraceptives, cyclosporin, and indinavir. In this report, we show that hyperforin, a constituent of St. John's wort with antidepressant activity, is a potent ligand (K(i) = 27 nM) for the pregnane X receptor, an orphan nuclear receptor that regulates expression of the cytochrome P450 (CYP) 3A4 monooxygenase. Treatment of primary human hepatocytes with hypericum extracts or hyperforin results in a marked induction of CYP3A4 expression. Because CYP3A4 is involved in the oxidative metabolism of >50% of all drugs, our findings provide a molecular mechanism for the interaction of St. John's wort with drugs and suggest that hypericum extracts are likely to interact with many more drugs than previously had been realized.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
The record
- Venue
- Proceedings of the National Academy of Sciences
- Topic
- Pharmacogenetics and Drug Metabolism
- Field
- Pharmacology, Toxicology and Pharmaceutics
- Canadian institutions
- —
- Funders
- —
- Keywords
- HyperforinHypericum perforatumPregnane X receptorCYP3A4HypericumPharmacologyHypericinPregnaneDrug metabolismChemistryCytochrome P450IndinavirNuclear receptorAngelica sinensisDrugMetabolismBiochemistryMedicineTraditional medicineTranscription factorStereochemistryHuman immunodeficiency virus (HIV)
- Has abstract in OpenAlex
- yes