DOI: 10.1073/pnas.130155097. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor

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

10.1073/pnas.130155097

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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.

Bibliography

Moore, L. B., Goodwin, B., Jones, S. A., Wisely, G. B., Serabjit-Singh, C. J., Willson, T. M., Collins, J. L., & Kliewer, S. A. (2000). St. Johnâs wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences, 97(13), 7500â7502.

Authors 8

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

References 22 Referenced 733

10.1136/bmj.313.7052.253
10.1055/s-2007-979522
10.1055/s-2007-979523
10.1055/s-2007-979342
10.1055/s-2007-979531
10.1016/S0024-3205(98)00299-9
10.1055/s-2007-979341
10.1016/S0304-3940(99)00087-7
10.1055/s-2007-979346
10.1007/s002280050519
10.1016/S0140-6736(99)00418-3
10.1016/S0140-6736(99)06457-0
10.1016/S0140-6736(99)05712-8
10.1016/S0140-6736(99)05467-7
P Maurel Cytochromes P450: Metabolic and Toxicological Aspects, ed C Ioannides (CRC, Boca Raton, FL), pp. 241–270 (1996). / Cytochromes P450: Metabolic and Toxicological Aspects by Maurel P (1996)
V Ramachandran, V E Kostrubsky, B J Komoroski, S Zhang, K Dorko, J E Esplen, S C Strom, R Venkataramanan Drug Metab Dispos 27, 1194–1199 (1999). / Drug Metab Dispos by Ramachandran V (1999)
10.1016/S0092-8674(00)80900-9
10.1172/JCI3703
10.1073/pnas.95.21.12208
10.1101/gad.12.20.3195
10.1210/mend.14.1.0409
10.1055/s-2007-979344

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:37 a.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 10:03 p.m.)
Indexed	1 week, 2 days ago (Aug. 28, 2025, 8:09 a.m.)
Issued	25 years, 2 months ago (June 13, 2000)
Published	25 years, 2 months ago (June 13, 2000)
Published Online	25 years, 2 months ago (June 13, 2000)
Published Print	25 years, 2 months ago (June 20, 2000)

Funders 0

None

BibTeX

@article{Moore_2000, title={St. John’s wort induces hepatic drug metabolism through activation of the pregnane X receptor}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.130155097}, DOI={10.1073/pnas.130155097}, number={13}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Moore, Linda B. and Goodwin, Bryan and Jones, Stacey A. and Wisely, G. Bruce and Serabjit-Singh, Cosette J. and Willson, Timothy M. and Collins, Jon L. and Kliewer, Steven A.}, year={2000}, month=jun, pages={7500–7502} }

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