title: Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model.
abstract: OBJECTIVE
  Resveratrol is a popular ingredient in dietary supplements. Some patients concomitantly use dietary supplements and medicines in Japan. In the present study, we determined whether trans-resveratrol and melinjo (Gnetum gnemon L.) seed extract (MSE), which contains resveratrol dimers, interacted with drugs using a mouse model.
  
  
  METHODS
  Male C57BL/6J mice were fed experimental diets containing 0.005%, 0.05%, or 0.5% (w/w) trans-resveratrol or MSE for 1 or 12 weeks. The expression of liver cytochrome P-450 (CYP) mRNA and activity of liver microsomal CYP were measured. To determine the influence of resveratrol or MSE on drug efficacy, the anticoagulant activity of warfarin was examined in mice that were fed diets containing trans-resveratrol or MSE for 12 weeks.
  
  
  RESULTS
  When the mice were fed experimental diets for 1 week, none of the doses of trans-resveratrol and MSE affected body weight, liver weight, or plasma AST and ALT levels. Trans-resveratrol also did not affect CYP1A1, CYP1A2, CYP2C, or CYP3A activities. In contrast, 0.5% MSE slightly increased CYP1A1 activity. When the mice were fed experimental diets for 12 weeks, 0.05% trans-resveratrol increased CYP1A1, CYP2C, and CYP3A activities, whereas 0.5% MSE suppressed CYP3A activity. Under these conditions, 0.5% trans-resveratrol enhanced the anticoagulant activity of warfarin, although CYP2C activity increased. However, MSE did not affect the anticoagulant activity of warfarin.
  
  
  CONCLUSIONS
  The 0.05% trans-resveratrol did not interact with warfarin in a mouse model, whereas 0.5% trans-resveratrol may have enhanced the anticoagulant activity of warfarin.
authors.affiliation: Information Center, National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Chiba
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kimura
authors.forename: Sachina
authors.initials: S
authors.lastname: Suzuki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Tatefuji
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D035684:Gnetum / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010936:Plant Extracts / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D000077185:Resveratrol; D012639:Seeds / Q000737:chemistry; D013267:Stilbenes / Q000494:pharmacology*; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D000975:Antioxidants; D004338:Drug Combinations; D010936:Plant Extracts; D013267:Stilbenes; D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D000077185:Resveratrol