Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice
Inhibition of Atherosclerotic Plaque Development by Oral Administration of α-Glucosyl Hesperidin and Water-Dispersible Hesperetin in Apolipoprotein E Knockout Mice
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DOI：
10.1080/07315724.2018.1468831
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发表时间：
2019-01-02
影响因子：
3.5
通讯作者：
Kitagawa, Tetsuya
中科院分区：
文献类型：
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作者：
Sugasawa, Noriko;Katagi, Ayako;Kitagawa, Tetsuya
目的：橙皮苷是柑橘果实中含量丰富的黄酮类化合物，其苷元橙皮素具有抗氧化、抗炎、降血脂、降血压等多种生理活性。在这项研究中，我们研究了α-葡萄糖基橙皮苷和水分散型橙皮素是否对载脂蛋白E基因敲除(Apo-E KO)小鼠的动脉粥样硬化进程具有保护作用。方法：10周龄雄性Apo-E KO小鼠随机分为常规高脂饲料、添加0.5%α-葡萄糖基橙皮苷的高脂饲料和添加0.1%水分散型橙皮素的高脂饲料，连续12周。通过测定血浆总胆固醇水平、主动脉根部组织学染色和巨噬细胞免疫组织化学方法评价动脉粥样硬化斑块的形成。同时测定了小鼠主动脉环的血管反应性。结果：α-葡萄糖基橙皮苷和水分散型橙皮苷均能降低血浆总胆固醇水平。它们还减少了斑块形成面积、脂肪沉积和巨噬细胞在动脉粥样硬化病变中的渗透。与高脂饮食组相比，两个实验饮食组对乙酰胆碱的血管内皮依赖性松弛反应都有所改善。结论：我们的研究表明，α-葡萄糖基橙皮苷和水分散体橙皮素对Apo-E KO小鼠的动脉粥样硬化进展具有保护作用，因为它们具有降血脂活性，通过巨噬细胞减少炎症，并防止内皮功能障碍。
Objective: Hesperidin, an abundant flavonoid in citrus fruit, and its aglycone, hesperetin, have been reported to possess various physiological activities, including antioxidant, anti-inflammatory, hypolipidemic, and antihypertensive activities. In this study, we investigated whether alpha-glucosyl hesperidin and water-dispersible hesperetin have protective effects on atherosclerotic progression in apolipoprotein E knockout (Apo-E KO) mice. Methods: Ten-week-old male Apo-E KO mice were randomly assigned a regular high-fat diet, a high-fat diet with 0.5% alpha-glucosyl hesperidin, or a high-fat diet with 0.1% water-dispersible hesperetin for 12 weeks. Measurement of plasma total cholesterol levels, histological staining of aortic root, and immunohistochemistry for macrophages were performed to evaluate atherosclerotic plaque formation. Vascular reactivity of mouse aortic rings was also measured. Results: Both alpha-glucosyl hesperidin and water-dispersible hesperetin reduced plasma total cholesterol level. They also reduced plaque formation area, adipose deposition, and macrophage infiltration into atherosclerotic lesion. Vascular-endothelium-dependent relaxation in response to acetylcholine was improved in both experimental diet groups compared to the high-fat diet group. Conclusions: Our study suggests that both alpha-glucosyl hesperidin and water-dispersible hesperetin exert protective effects on atherosclerotic progression in Apo-E KO mice because they exhibit hypolipidemic activity, reduce inflammation through macrophages, and prevent endothelial dysfunction.