Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice

Safflower yellow ameliorates cognition deficits and reduces tau phosphorylation in APP/PS1 transgenic mice
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红花黄可改善 APP/PS1 转基因小鼠的认知缺陷并减少 tau 磷酸化

DOI:
10.1007/s11011-016-9857-3
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发表时间:
2016-06
影响因子:
3.6
通讯作者:
Hu Yan-li
Hu Yan-li
中科院分区:
医学3区
文献类型:
--
作者:
Ruan Ying-ying;Zhai Wei;Shi Xiao-meng;Zhang Lu;Hu Yan-li

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阿尔茨海默病(AD)是世界范围内最常见的痴呆病因,其主要特征是聚集的β-淀粉样蛋白(Aβ)和过度磷酸化的tau。红花黄(SY)是一种从天然红花中提取的新的水提取物,已被认为可以改善几种痴呆动物模型的记忆缺陷。本研究旨在探讨Syon对APP/PS1双转基因小鼠学习记忆障碍和tau蛋白过度磷酸化的影响及其机制。APP/PS1小鼠于6月龄时灌胃给予SY(10、30、100 mg/kg),共3个月。用跳台实验和Morris水迷宫实验检测小鼠的学习记忆能力,用免疫印迹法检测大鼠脑内蛋白质水平。在这里,我们发现SY治疗可以改善APP/PS1小鼠的空间学习记忆能力,并减少tau蛋白在Ser199、Thr205、Ser396、Ser404位点的过度磷酸化。此外,SY还能显著降低APP/PS1小鼠细胞周期蛋白依赖性激酶5(CDK5)和糖原合成酶激酶3β(GSK 3β)的活性。这些结果支持SY有望成为治疗AD的一种多靶点神经治疗剂。
Alzheimer’s disease (AD), the most common cause of dementia worldwide, is mainly characterized by the aggregated β-amyloid (Aβ) and hyperphosphorylated tau. Safflower yellow (SY) is a novel water extract of natural safflower and has been suggested to ameliorate memory deficits.in several animal models of dementia. In this study, we aimed to investigate the effect andmechanismof SYon deficits of learning and memory and hyperphosphorylation of tau in APP/PS1 double transgenic mice. APP/PS1 mice were administered with SY (10, 30, 100 mg/kg) by oral gavage.for three months at the age of six months. The ability of learning and memory was investigated using the step-down test and Morris water maze test, and protein level in the brain was evaluated using western blot. Here, we found that SY treatment can improve spatial learning and memory ability,.and reduce tau hyperphosphorylation at Ser199, Thr205, Ser396, Ser404 sites in APP/PS1mice. In addition, the activity the of cyclin-dependent kinase 5 (CDK-5) and glycogen synthase kinase 3β (GSK-3β), major kinases involved in tau phosphorylation, was siginificantly decreased in APP/PS1 mice by SY treatment. These results support SY can serve as a promising multitarget neuronal therapeutic agent for the treatment of AD.
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