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0090-9556/04/3201-28-34$20.00
DMD 32:28-34, 2004

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IN VITRO METABOLISM OF HYPERFORIN IN RAT LIVER MICROSOMAL SYSTEMS

Yanyan Cui, Catharina Y.W. Ang, Richard D. Beger, Thomas M. Heinze, Lihong Hu, and Julian Leakey

National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas

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.

Address correspondence to: Catharina Y.W. Ang, HFT-230, Division of Chemistry, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079. E-mail: Cang{at}NCTR.FDA.GOV




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