title: Effects of Seijo-bofu-to, a traditional Japanese herbal medicine containing furanocoumarin derivatives, on the drug-metabolizing enzyme activities in healthy male volunteers.
abstract: Seijo-bofu-to, a traditional medicine used to treat acne in Asian countries, contains twelve herbal components, including Angelica dahurica root, a source of furanocoumarin derivatives. In this study, we investigated potential herb-drug interactions of seijo-bofu-to in healthy male volunteers. Thirty-two young, healthy, non-smoking males were assessed for the baseline activity of cytochrome P450 (CYP) 1A2, CYP3A, CYP2D6, N-acetyltransferase 2 and xanthine oxidase according to the urinary metabolic indices of 8-hr urine samples collected after the administration of a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan, and the ratio of urinary excretion of 6β-hydroxycortisol to cortisol. Thereafter, the volunteers received 3.75 g of seijo-bofu-to twice daily for 7 days and underwent the same tests on post-dose day 7. The geometric mean ratio of the CYP1A2 activity on day 7 to that observed at baseline was 0.66 (95% CI, 0.55-0.79, p = 0.001). The geometric mean phenotypic indices for CYP3A, CYP2D6, N-acetyltransferase 2 and xanthine oxidase on day 7 did not differ from the baseline values. The findings of the present study suggest that seijo-bofu-to may inhibit the activity of CYP1A2, whereas it is unlikely to participate in herb-drug interactions involving medications predominantly metabolized by CYP3A, CYP2D6, N-acetyltransferase 2 or xanthine oxidase.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.forename: Ayaka
authors.initials: A
authors.lastname: Takashima
authors.forename: Kousuke
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hiromi
authors.initials: H
authors.lastname: Soraoka
authors.forename: Tong-Bin
authors.initials: TB
authors.lastname: Ding
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uchiyashiki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Motoki
authors.initials: M
authors.lastname: Imamura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.forename: Keishi
authors.initials: K
authors.lastname: Miyata
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000328:Adult; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism; D044466:Asian People; D002110:Caffeine / Q000008:administration & dosage; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D003915:Dextromethorphan / Q000008:administration & dosage; D011564:Furocoumarins / Q000494:pharmacology*; D064368:Healthy Volunteers; D041743:Herb-Drug Interactions; D029001:Herbal Medicine; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D008519:Medicine, Traditional; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry; D014969:Xanthine Oxidase / Q000378:metabolism; D055815:Young Adult
chemical_list: D011564:Furocoumarins; D002110:Caffeine; C001380:6 beta-hydroxycortisol; D003915:Dextromethorphan; C504573:CYP1A2 protein, human; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; D014969:Xanthine Oxidase; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D006854:Hydrocortisone