Document Detail

Effect of 7-difluoromethyl-5, 4'-dimethoxygenistein on aorta atherosclerosis in hyperlipidemia ApoE(-/-) mice induced by a cholesterol-rich diet.
MedLine Citation:
PMID:  23589679     Owner:  NLM     Status:  MEDLINE    
PURPOSE: 7-Difluoromethyl-5, 4'-dimethoxygenistein (DFMG), prepared by the difluoromethylation and alkylation of Genistein, is an active new chemical entity. Its anti-atherosclerosis effect was found in a series of studies in vitro. In this article, we explored and evaluated the anti-atherosclerosis effect via its protection of endothelial function in ApoE(-/-) mice that were fed a high-fat diet.
METHODS: Five C57BL/6J mice were selected as a control group and were fed a 1% high-fat diet (control group, n = 5). Five ApoE(-/-) mice that were fed a high-fat diet for 16 weeks were selected as the atherosclerosis model group (model group, n = 5). In the phase I study, 25 ApoE(-/-) mice were provided a prophylactic treatment with different drugs at the beginning of the 16 week high-fat diet: 5 mg/gk genistein (genistein 1 group, n = 5), 5 mg/kg lovastatin (lovastatin1 group, n = 5), 2.5 mg/kg DFMG (DFMG L1 group, n = 5), 5 mg/kg DFMG (DFMG M1 group, n = 5), and 10 mg/kg DFMG (DFMG H1 group, n = 5). In the phase II study, 25 atherosclerosis model, ApoE(-/-) mice were treated with different drugs and fed a high-fat diet for 16 weeks: 5 mg/gk genistein (genistein 2 group, n = 5), 5 mg/kg lovastatin (lovastatin 2 group, n = 5), 2.5 mg/kg DFMG (DFMG L2 group, n = 5), 5 mg/kg DFMG (DFMG M2 group, n = 5), and 10 mg/kg DFMG (DFMG H2 group, n = 5). The plasma levels of lipids, von Willebrand factor (vWF), and nitrite were compared between phases I and II. Endothelium-dependent relaxation (EDR), aortic lesion development, and quantification in thoracic aortas were measured during these two phase studies.
RESULTS: Compared to the model group, the lipid and vWF plasma levels were significantly lower, the plasma nitrite levels were significantly higher, the fatty streaks of aortic lesions were significantly lower, and the endothelium dependent relaxation was significantly higher after both phase studies (P < 0.05). The DFMG supplementation led to significant plasma nitrite increment in all groups after both phase studies (P < 0.05). There were significantly decreased fatty streaks of aortic lesions in DFMG-prevented and DFMG-treated mice (P < 0.05). There was a significant increase in EDR in all prophylactic treatment groups and treatment groups (P < 0.05). We further demonstrated that the preventative effect was more obvious than the therapeutic effect.
CONCLUSION: Our results suggest that DFMG could work in prophylactic and therapeutic treatments for atherosclerosis development.
Yong Zhang; Lesai Li; Jiliang You; Jianguo Cao; Xiaohua Fu
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-04-03
Journal Detail:
Title:  Drug design, development and therapy     Volume:  7     ISSN:  1177-8881     ISO Abbreviation:  Drug Des Devel Ther     Publication Date:  2013  
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-06-13     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101475745     Medline TA:  Drug Des Devel Ther     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  233-42     Citation Subset:  IM    
Department of Hematology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
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MeSH Terms
Aorta, Thoracic / drug effects,  pathology
Apolipoproteins E / genetics*
Atherosclerosis / drug therapy*,  pathology
Diet, High-Fat
Disease Models, Animal
Dose-Response Relationship, Drug
Endothelium, Vascular / drug effects,  metabolism
Genistein / administration & dosage,  analogs & derivatives*,  pharmacology
Hyperlipidemias / drug therapy*
Lipids / blood
Lovastatin / pharmacology
Mice, Inbred C57BL
Mice, Knockout
Nitrites / metabolism
Vasodilation / drug effects
von Willebrand Factor / drug effects,  metabolism
Reg. No./Substance:
0/7-difluoromethyl-5,4'-dimethoxygenistein; 0/Apolipoproteins E; 0/Lipids; 0/Nitrites; 0/von Willebrand Factor; 446-72-0/Genistein; 75330-75-5/Lovastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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