Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice
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雷公藤甲素可防止 APP/PS1 小鼠的记忆缺陷和淀粉样蛋白 β 聚集，同时抑制炎症和 MAPK 活性。
DOI：
10.2174/156720501303160217122803
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Wang, Xiao-Min
中科院分区：
文献类型：
--
作者：
Cui, Yan-Qiu;Wang, Qi;Wang, Xiao-Min
阿尔茨海默病（Alzheimer's disease，AD）是一种以β-淀粉样蛋白（amyloid-beta，A β）聚集于海马和大脑皮质为特征的神经退行性疾病。神经炎症被认为是AD认知功能下降进展的驱动力。在神经炎症过程中，A β肽诱导活化的星形胶质细胞和小胶质细胞产生促炎因子和神经毒素，促进AD脑神经退行性变，最终导致痴呆。因此，抑制AD脑中胶质细胞的过度激活可能会产生治疗作用。雷公藤内酯醇是从中草药雷公藤中提取的天然化合物，已经显示出抗炎作用。雷公藤内酯醇是否通过抗炎作用对AD样病理表现出预防作用尚不清楚。本研究表明，腹腔注射雷公藤内酯醇（20 μ g/kg）15周，显著减轻了AD转基因小鼠（APP/PS1小鼠）的学习和记忆缺陷，并防止了A β在脑中的积累。与盐水处理的APP/PS1小鼠相比，雷公藤内酯醇处理的APP/PS1小鼠脑中的胶质细胞活化和促炎因子含量减少。此外，我们还观察到雷公藤内酯醇对APP/PS1小鼠脑内丝裂原活化蛋白激酶（MAPK，包括p38、ERK和JNK）磷酸化的抑制作用。总之，我们的研究表明，雷公藤内酯醇对AD模型的治疗作用的分子机制可能涉及通过抑制MAPKs活性来抑制神经炎症。
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-beta (A beta) peptide in the hippocampus and cortex of brain. Neuroinflammation is considered a driving force of the progression of cognitive decline in AD. During the neuroinflammatory process, activated astrocytes and microglia induced by A beta peptide produce pro-inflammatory factors and neurotoxins, which promote neurodegeneration in AD brain, eventually dementia. Thus, the suppression of glial over-activation in AD brain might result in therapeutic effect. Triptolide, a natural compound extracted from the Chinese medicinal herb Tripterygium wilfordii Hook F., has shown anti-inflammatory effects. Whether triptolide exhibits preventive effects on AD-like pathology via anti-inflammatory action is unclear. The present study showed that intraperitoneal injection of triptolide (20 mu g/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented A beta accumulation in the brain of AD transgenic mice (APP/PS1 mice). These results were accompanied by reduction in glial activation and contents of pro-inflammatory factors in the brain of APP/PS1 mice treated by triptolide compared to saline-treated APP/PS1 mice. In addition, we observed that the Mitogen-activated protein kinases (MAPKs, including p38, ERK and JNK) phosphorylation was also suppressed by treatment of triptolide in the brain of APP/PS1 mice. Taken together, our study suggests that molecular mechanisms underlying the therapeutic effects of triptolide on the AD model might involve inhibition of the neuroinflammation by suppressing MAPKs activity.