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首页> 外文期刊>The Journal of Nutritional Biochemistry >Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice.
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Naringin, the major grapefruit flavonoid, specifically affects atherosclerosis development in diet-induced hypercholesterolemia in mice.

机译：主要的柚子类黄酮柚皮苷特别影响饮食引起的小鼠高胆固醇血症的动脉粥样硬化发展。

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摘要

Naringin (NAR) from grapefruit has exhibited potential protective effects against atherosclerosis development. However, specific mechanisms responsible for such effects are poorly understood. Thus, we aimed to investigate the antiatherogenic effects of NAR in different mouse models of hypercholesterolemia and decipher its molecular targets in the aorta using transcriptomic approach. Two mouse models of hypercholesterolemia, wild-type mice fed a high-fat/high-cholesterol diet and apolipoprotein E-deficient mice fed a semisynthetic diet, were studied. Mice were fed a respective control diets supplemented or not for 18 weeks with 0.02% of NAR, that is, nutritional supplementation. NAR supplementation reduced plaque progression only in wild-type mice fed the high-fat/high-cholesterol diet (-41%). Consistent with this protective effect, NAR reduced plasma non-high-density lipoprotein cholesterol concentrations as well as biomarkers of endothelial dysfunction. Microarray studies performed on aortas demonstrated differentially expressed genes encoding proteins involved in cell adhesion, actin cytoskeleton organization and cell division. Thus, the changes in gene expression induced by NAR could suggest a limited atherosclerosis progression by preventing immune cell adhesion and infiltration in the intima of vascular wall, as well as smooth muscle cell proliferation. Furthermore, this hypothesis was strengthened by in vitro experiments, which showed the ability of naringenin to reduce monocyte adhesion to endothelial cells and smooth muscle cell proliferation. In conclusion, this study revealed the antiatherogenic effect of NAR supplemented at a nutritionally achievable dose, specifically toward diet-induced atherosclerosis, and depicted its multitarget mode of action at the vascular level
机译：葡萄柚的柚皮苷（NAR）对动脉粥样硬化的发展具有潜在的保护作用。但是，引起这种影响的具体机制了解甚少。因此，我们旨在研究NAR在高胆固醇血症的不同小鼠模型中的抗动脉粥样硬化作用，并使用转录组学方法来分析其在主动脉中的分子靶标。研究了两种高胆固醇血症的小鼠模型，高脂/高胆固醇饮食的野生型小鼠和半合成饮食的载脂蛋白E缺乏症的小鼠。分别给小鼠补充或不补充0.02％NAR（即营养补充）的对照饮食。 NAR补充仅在高脂/高胆固醇饮食（-41％）的野生型小鼠中减少了斑块进展。与这种保护作用一致，NAR降低了血浆非高密度脂蛋白胆固醇的浓度以及内皮功能障碍的生物标志物。在主动脉上进行的微阵列研究表明，差异表达的基因编码的蛋白质参与细胞粘附，肌动蛋白细胞骨架组织和细胞分裂。因此，由NAR诱导的基因表达变化可能通过阻止免疫细胞粘附和血管壁内膜浸润以及平滑肌细胞增殖而提示有限的动脉粥样硬化进展。此外，这一假说通过体外实验得到了证实，该实验表明柚皮苷具有减少单核细胞粘附于内皮细胞和平滑肌细胞增殖的能力。总之，这项研究揭示了以营养可实现的剂量补充NAR的抗动脉粥样硬化作用，特别是对饮食诱发的动脉粥样硬化，并描述了其在血管水平上的多靶点作用方式

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