%0 Journal Article %A Yanyan Cui %A Catharina Y.W. Ang %A Richard D. Beger %A Thomas M. Heinze %A Lihong Hu %A Julian Leakey %T IN VITRO METABOLISM OF HYPERFORIN IN RAT LIVER MICROSOMAL SYSTEMS %D 2004 %R 10.1124/dmd.32.1.28 %J Drug Metabolism and Disposition %P 28-34 %V 32 %N 1 %X 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. The American Society for Pharmacology and Experimental Therapeutics %U https://dmd.aspetjournals.org/content/dmd/32/1/28.full.pdf