Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer's Disease.
Royal Jelly Reduces Cholesterol Levels, Ameliorates Aβ Pathology and Enhances Neuronal Metabolic Activities in a Rabbit Model of Alzheimer's Disease.
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DOI：
10.3389/fnagi.2018.00050
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发表时间：
2018
影响因子：
4.8
通讯作者：
Hu F
中科院分区：
文献类型：
--
作者：
Pan Y;Xu J;Chen C;Chen F;Jin P;Zhu K;Hu CW;You M;Chen M;Hu F
阿尔茨海默病（Alzheimer's disease，AD）是以β淀粉样蛋白（amyloid β，Aβ）聚集和神经元丢失为特征的最常见的痴呆形式。AD的风险因素之一是高胆固醇水平，已知其可促进Aβ沉积。以往的研究表明，工蜂的产物皇家浆（RJ）具有潜在的神经保护作用，可以减弱Aβ毒性。然而，关于RJ如何调节Aβ形成及其对胆固醇水平和神经元代谢活动的影响知之甚少。在此，我们研究了RJ是否可以降低2%胆固醇饮食加铜饮用水诱导的AD兔模型的胆固醇水平，调节Aβ水平和增强神经元代谢活动。结果表明，RJ能显著降低家兔血浆总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平，降低脑内Aβ水平。Aβ免疫组化和Thioflavin-T染色结果显示，RJ能明显改善AD兔的淀粉样蛋白沉积。此外，RJ还能降低β-site APP cleaving enzyme-1（BACE 1）和晚期糖基化终产物受体（receptor for advanced glycation end products，RECE 1）的表达，提高低密度脂蛋白受体相关蛋白1（low density lipoprotein receptor-related protein 1，LRP-1）和胰岛素降解酶（insulin degrading enzyme，IDE）的表达。此外，我们发现RJ显着增加AD兔的神经元数量，增强抗氧化能力，抑制激活的半胱氨酸蛋白酶-3蛋白表达，并通过增加N-乙酰天冬氨酸（NAA）和谷氨酸，减少胆碱和肌醇增强神经元代谢活动。综上所述，我们的数据表明，RJ可以降低AD兔的胆固醇水平，调节Aβ水平并增强神经元代谢活性，为RJ治疗具有保护神经元和预防AD的潜力提供了临床前证据。
Alzheimer’s disease (AD) is the most common form of dementia characterized by aggregation of amyloid β (Aβ) and neuronal loss. One of the risk factors for AD is high cholesterol levels, which are known to promote Aβ deposition. Previous studies have shown that royal jelly (RJ), a product of worker bees, has potential neuroprotective effects and can attenuate Aβ toxicity. However, little is known about how RJ regulates Aβ formation and its effects on cholesterol levels and neuronal metabolic activities. Here, we investigated whether RJ can reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in an AD rabbit model induced by 2% cholesterol diet plus copper drinking water. Our results suggest that RJ significantly reduced the levels of plasma total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C), and decreased the level of Aβ in rabbit brains. RJ was also shown to markedly ameliorate amyloid deposition in AD rabbits from Aβ immunohistochemistry and thioflavin-T staining. Furthermore, our study suggests that RJ can reduce the expression levels of β-site APP cleaving enzyme-1 (BACE1) and receptor for advanced glycation end products (RAGE), and increase the expression levels of low density lipoprotein receptor-related protein 1 (LRP-1) and insulin degrading enzyme (IDE). In addition, we found that RJ remarkably increased the number of neurons, enhanced antioxidant capacities, inhibited activated-capase-3 protein expression, and enhanced neuronal metabolic activities by increasing N-acetyl aspartate (NAA) and glutamate and by reducing choline and myo-inositol in AD rabbits. Taken together, our data demonstrated that RJ could reduce cholesterol levels, regulate Aβ levels and enhance neuronal metabolic activities in AD rabbits, providing preclinical evidence that RJ treatment has the potential to protect neurons and prevent AD.
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影响因子：
3.7
作者：
Chen SM;Fan CC;Chiue MS;Chou C;Chen JH;Hseu RS
通讯作者：
Hseu RS
影响因子：
1.2
作者：
Hattori, Noriko;Nomoto, Hiroshi;Furukawa, Shoei
通讯作者：
Furukawa, Shoei
影响因子：
105.7
作者：
Kivipelto, M;Helkala, EL;Nissien, A
通讯作者：
Nissien, A
影响因子：
2.8
作者：
Fereshtehnejad, Seyed-Mohammad;Johnell, Kristina;Eriksdotter, Maria
通讯作者：
Eriksdotter, Maria
影响因子：
2.4
作者：
Chen, Shuang-Qing;Wang, Pei-Jun;Zang, Feng-Chao
通讯作者：
Zang, Feng-Chao