7-Difluoromethyl-5,4'-dimethoxygenistein, a novel genistein derivative, has therapeutic effects on atherosclerosis in a rabbit model.
Genistein is a phytoestrogen that is known to have a protective effect on the vascular endothelial wall. However, it exhibits poor bioavailability, which limits the use of genistein to treat cardiovascular and cerebrovascular diseases. A novel genistein derivative, 7-difluoromethyl-5,4'-dimethoxygenistein (dFMGEN), has shown a better protective effect on vascular endothelial damage in vitro than genistein. In this study, we further evaluated therapeutic effects of dFMGEN on the vascular endothelial wall and atherosclerosis in a rabbit model in vivo. There were 5 groups: the GEN group (genistein 5 mg/kg per day), lovastatin group (lovastatin 5 mg/kg per day), dFMGEN group (dFMGEN 5 mg/kg per day), model control group (the same amount of vehicle solvent), and the normal control group; all feedings administered via intragastric administration. We demonstrated that dFMGEN (1) attenuated the development of atherosclerosis, (2) reduced serum total cholesterol and low-density lipoprotein cholesterol concentrations, (3) decreased lipid peroxidation in the rabbit atherosclerosis model, and (4) increased smooth muscle cell and collagen content in atheroma of thoracic aortas. These results provide an experimental foundation for dFMGEN's potential effects in preventing and treating atherosclerosis, acute coronary syndromes, and potentially ischemia-reperfusion injury during acute myocardial infarction and cerebral infarction.
Zhao
Hong
H
Hunan Normal University, Changsha, China.
Li
Cheng
C
Cao
Jian-Guo
JG
Xiang
Hong-Lin
HL
Yang
Hua-Zhong
HZ
You
Ji-Liang
JL
Li
Cheng-Long
CL
Fu
Xiao-Hua
XH
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019833:Genistein / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015227:Lipid Peroxidation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D048789:Phytoestrogens / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits
C541079:7-difluoromethyl-5,4'-dimethoxygenistein; D008077:Lipoproteins, LDL; D048789:Phytoestrogens; D003094:Collagen; D002784:Cholesterol; D019833:Genistein