title: Inhibitory effect of natural furanocoumarins on human microsomal cytochrome P450 3A activity.
abstract: To investigate the possible drug interaction with herbal medicine, furanocoumarin derivatives isolated from several Umbelliferous crude drugs were examined for their inhibitory effects on a typical human drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Most furanocoumarins tested at 0.1 mM reduced microsomal testosterone 6beta-hydroxylation as an index of CYP3A activity to less than 50% of the control. In particular, the dimer and trimer derivatives of furanocoumarins showed striking inhibition, whose potencies were similar to that of a typical CYP3A inhibitor, ketoconazole. Preincubation of dimer types of furanocoumarins increased suppression but not most of the monomer derivatives, suggesting that the inhibition on CYP3A activity was caused by at least plural mechanisms. These results raised the possibility that the furanocoumarin containing herbal medicines may alter pharmacokinetics of co-ingested drugs similar to the case with grapefruit juice.
authors.affiliation: Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: L Q
authors.initials: LQ
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Xiao
authors.forename: K
authors.initials: K
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Ohta
authors.forename: Y
authors.initials: Y
authors.lastname: Yamazoe
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D003374:Coumarins / Q000494:pharmacology*; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000201:enzymology*; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D010946:Plants, Medicinal; D013329:Structure-Activity Relationship
chemical_list: D003374:Coumarins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating