RT Journal Article
SR Electronic
T1 IN VITRO METABOLISM OF HYPERFORIN IN RAT LIVER MICROSOMAL SYSTEMS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 28
OP 34
DO 10.1124/dmd.32.1.28
VO 32
IS 1
A1 Yanyan Cui
A1 Catharina Y.W. Ang
A1 Richard D. Beger
A1 Thomas M. Heinze
A1 Lihong Hu
A1 Julian Leakey
YR 2004
UL http://dmd.aspetjournals.org/content/32/1/28.abstract
AB 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