title: In vitro metabolism of hyperforin in rat liver microsomal systems.
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.
authors.affiliation: National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Cui
authors.forename: Catharina Y W
authors.initials: CY
authors.lastname: Ang
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Heinze
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
authors.forename: Julian
authors.initials: J
authors.lastname: Leakey
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001711:Biotransformation; D001643:Bridged Bicyclo Compounds; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006900:Hydroxylation; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013729:Terpenes / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001643:Bridged Bicyclo Compounds; D006993:Hypnotics and Sedatives; D013729:Terpenes; D009243:NAD; D003907:Dexamethasone; D010696:Phloroglucinol; C001654:hyperforin; D010634:Phenobarbital