St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor

Linda B. Moore, Bryan Goodwin, Stacey A. Jones, G. Bruce Wisely, Cosette J. Serabjit-Singh, Timothy M. Willson, Jon L. Collins, Steven A. Kliewer

Research output: Contribution to journalArticle

806 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7500-7502
Number of pages3
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number13
DOIs
StatePublished - Jun 20 2000

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