Atheroprotective and plaque-stabilizing effects of enzymatically modified isoquercitrin in atherogenic apoE-deficient mice

Abstract

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. Conclusion EMIQ has atheroprotective and plaque-stabilizing effects.