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Trans-Resveratrol Enhances the Anticoagulant Activity of Warfarin in a Mouse Model
- Source :
- Journal of Atherosclerosis and Thrombosis. 23:1099-1110
- Publication Year :
- 2016
- Publisher :
- Japan Atherosclerosis Society, 2016.
-
Abstract
- Aim 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. Conclusion 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.
- Subjects :
- 0301 basic medicine
Drug
CYP3A
media_common.quotation_subject
Resveratrol
Pharmacology
Efficacy
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal Medicine
medicine
media_common
business.industry
organic chemicals
Biochemistry (medical)
CYP1A2
Warfarin
food and beverages
body regions
030104 developmental biology
Real-time polymerase chain reaction
chemistry
030220 oncology & carcinogenesis
Microsome
Cardiology and Cardiovascular Medicine
business
medicine.drug
Subjects
Details
- ISSN :
- 18803873 and 13403478
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Journal of Atherosclerosis and Thrombosis
- Accession number :
- edsair.doi...........01c2e55cd7e52b4d7bbddf8cce427614