Abstract
Hyperforin is an important active component of St. John's wort (Hypericum perforatum) that has been suggested to be responsible for the St. John's wort antidepressive effects and herbal-drug interactions. In this study, the in vitro metabolism profile of hyperforin was investigated using liver microsomes from male and female Sprague-Dawley rats, with or without induction by phenobarbital or dexamethasone. Four major Phase I metabolites, named 19-hydroxyhyperforin, 24-hydroxyhyperforin, 29-hydroxyhyperforin, and 34-hydroxyhyperforin, were isolated by high performance liquid chromatography and identified by mass spectrometry and NMR. Results suggest that hydroxylation is a major biotransformation of the hyperforin pathway in rat liver and that inducible cytochrome P450 3A (CYP450 3A) and/or CYP2B may be the major cytochrome P450 isoforms catalyzing these hydroxylation reactions.
Footnotes
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↵1 Abbreviations used are: HPLC/MS, high performance liquid chromatography/mass spectrometry; PDA, photodiode array detection; P450, cytochrome P450; ACN, acetonitrile; LC/ESI MS, liquid chromatography/electrospray ionization mass spectrometry; NOESY, nuclear Overhauser effect spectroscopy; COSY, correlation spectroscopy; TOCSY, total correlation spectroscopy; HSQC, heteronuclear single quantum correlation; HMBC, heteronuclear multiple-bond correlation spectroscopy.
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Yanyan Cui was supported by an appointment to the ORAU Research Program at the National Center for Toxicological Research, administered by the Oak Ridge Associated Universities through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.
- Received May 9, 2003.
- Accepted August 28, 2003.
- The American Society for Pharmacology and Experimental Therapeutics
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