Fuzheng Quxie Decoction Ameliorates Learning and Memory Impairment in SAMP8 Mice by Decreasing Tau Hyperphosphorylation.
Fuzheng Quxie Decoction Ameliorates Learning and Memory Impairment in SAMP8 Mice by Decreasing Tau Hyperphosphorylation.
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扶正祛邪汤通过减少 Tau 过度磷酸化改善 SAMP8 小鼠学习和记忆障碍
DOI：
10.1155/2017/5934254
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Yang Y;Jia X;Feng J;Wang Z;Cao Y;Liu J;Li H
微管相关蛋白tau的过度磷酸化对阿尔茨海默病（AD）的进展至关重要。扶正祛邪汤是治疗AD的有效方剂。在本研究中，我们采用高效液相色谱和液相色谱串联质谱法来鉴定FQD的组分。三种主要成分（C5 Rg 1，C5 RRe和黄连碱）在喂食C5 RD的小鼠的大脑中被检测到，表明它们能够穿过血脑屏障。我们进一步评估了FQD对衰老加速小鼠Prone-8（SAMP 8）小鼠的功效。FQD显著改善SAMP 8小鼠在Morris水迷宫上的学习和记忆缺陷，减少逃避潜伏期（p < 0.01），增加在原始平台象限内的游泳时间（p < 0.05）。此外，FQD增加海马CA 1区神经元和神经元内尼氏体的数量。FQD还降低磷酸化tau蛋白的表达，并增加蛋白磷酸酶2A（PP 2A）和N-甲基-D-天冬氨酸受体亚单位NR 2A的表达（p < 0.01）。本研究结果表明，FQD改善SAMP 8小鼠的学习记忆能力。此外，我们的研究结果表明，FQD的保护作用可能是通过抑制海马tau蛋白过度磷酸化介导的NMDAR/PP 2A相关蛋白。
Hyperphosphorylation of the microtubule-associated protein, tau, is critical to the progression of Alzheimer's disease (AD). Fuzheng Quxie Decoction (FQD), a Chinese herbal complex, is an effective clinical formula used to treat AD. In the current study, we employed high-performance liquid chromatography and liquid chromatography tandem mass spectrometry to identify the components of FQD. Three major components (ginsenoside Rg1, ginsenoside Re, and coptisine) were detected in the brain of FQD-fed mice, indicating their ability to cross the blood-brain barrier. We further evaluated the efficacy of FQD on Senescence-Accelerated Mice Prone-8 (SAMP8) mice. FQD significantly ameliorated learning and memory deficits in SAMP8 mice on the Morris Water Maze, decreasing escape latency (p < 0.01) and increasing swim time within the original platform-containing quadrant (p < 0.05). Further, FQD increased the number of neurons and intraneuronal Nissl bodies in the hippocampal CA1 region. FQD also decreased the expression of phosphorylated tau protein and increased the expression of protein phosphatase 2A (PP2A) and the N-methyl-D-aspartate receptor subunit, NR2A (p < 0.01). Our results indicate that FQD improves the learning and memory ability of SAMP8 mice. Moreover, our findings suggest that the protective effect of FQD is likely mediated through an inhibition of hippocampal tau hyperphosphorylation via NMDAR/PP2A-associated proteins.
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