title: Hepatic cytochrome P450 mediates interaction between warfarin and Coleus forskohlii extract in vivo and in vitro.
abstract: OBJECTIVE
  This study aimed to determine whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo and its relationship with hepatic cytochrome P450 (CYP).
  
  
  METHODS
  Mice were fed various doses of CFE standardised with 10% forskolin in a normal diet for one week, or in protein diets containing 7% and 20% casein (low and normal) for four weeks. They were then administered with warfarin by gavage on the last two days of the treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were analysed at 18 h after the last dose. Direct interaction between CFE and forskolin with CYP2C was evaluated in vitro.
  
  
  RESULTS
  CFE dose dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%. Warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. The findings were similar in mice fed diets containing CFE and different ratios of protein. CFE directly inhibited CYP2C activity in mouse and human liver microsomes in vitro, whereas forskolin was only slightly inhibitory.
  
  
  CONCLUSIONS
  CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE.
authors.affiliation: Information Center, National Institute of Health and Nutrition, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yokotani
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Yoko
authors.initials: Y
authors.lastname: Sato
authors.forename: Yuko
authors.initials: Y
authors.lastname: Taki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shinozuka
authors.forename: Masatsune
authors.initials: M
authors.lastname: Murata
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D002364:Caseins / Q000008:administration & dosage; D031330:Coleus / Q000737:chemistry*; D005576:Colforsin / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D004044:Dietary Proteins / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D041743:Herb-Drug Interactions; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008862:Microsomes, Liver / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D014859:Warfarin / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D002364:Caseins; D004044:Dietary Proteins; D010936:Plant Extracts; D005576:Colforsin; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System