TY - JOUR T1 - IN VITRO METABOLISM OF HYPERFORIN IN RAT LIVER MICROSOMAL SYSTEMS JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 28 LP - 34 DO - 10.1124/dmd.32.1.28 VL - 32 IS - 1 AU - Yanyan Cui AU - Catharina Y.W. Ang AU - Richard D. Beger AU - Thomas M. Heinze AU - Lihong Hu AU - Julian Leakey Y1 - 2004/01/01 UR - http://dmd.aspetjournals.org/content/32/1/28.abstract N2 - 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 ER -