Atheroprotective and plaque-stabilizing effects of enzymatically modified isoquercitrin in atherogenic apoE-deficient mice.
OBJECTIVE
Enzymatically modified isoquercitrin (EMIQ), isoquercitrin with malto-oligosaccharides, has been recognized as "generally recognized as safe" by the Flavor and Extracts Manufacturers Association in the United States since 2003. The long-term antiatherogenic effect of EMIQ was examined using apolipoprotein E (apoE)-deficient atherogenic mice.


METHODS
Male apoE-deficient mice (6 wk old) were fed with a high-fat diet alone or a diet containing EMIQ for 14 wk. At 20 wk old, atherosclerotic lesions in the aorta and aortic sinus were measured by morphometry and histomorphometry.


RESULTS
In apoE-deficient mice, EMIQ did not significantly affect body weight, plasma total cholesterol, triacylglycerol, and high-density lipoprotein cholesterol throughout the experiment. EMIQ significantly suppressed the aortic atherosclerotic lesion area (control 8.8 +/- 3.5% versus EMIQ 4.4 +/- 1.5%, mean +/- SD, P = 0.022). Similarly, atherosclerotic plaque lesions in the aortic sinus were significantly reduced by EMIQ (control 37.7 +/- 3.6% versus EMIQ 30.2 +/- 2.0%, P = 0.010). Of note, the immunostained area for macrophage or 4-hydroxy-2-nonenal, a well-recognized marker of oxidative stress, at the plaque in the aortic sinus was markedly suppressed, whereas the area for collagen or smooth muscle cell were increased by EMIQ, suggesting a plaque-stabilizing effect of EMIQ.


CONCLUSIONS
EMIQ has atheroprotective and plaque-stabilizing effects.
Motoyama
Koka
K
Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Koyama
Hidenori
H
Moriwaki
Masamitsu
M
Emura
Kazuhiro
K
Okuyama
Shuji
S
Sato
Eisuke
E
Inoue
Masayasu
M
Shioi
Atsushi
A
Nishizawa
Yoshiki
Y
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012850:Sinus of Valsalva / Q000503:physiopathology; D029909:Sophora; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D009844:Oligosaccharides; D014280:Triglycerides; D002784:Cholesterol; D011794:Quercetin