雷公藤内酯醇救援空间记忆障碍和淀粉样蛋白β聚集伴随在APP/PS1转基因小鼠的炎症反应和蛋白激酶活性的抑制反应

Title:Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice

Volume: 13 Issue: 3

Author(s): Yan-Qiu Cui, Qi Wang, Dong-Mei Zhang, Jun-Ya Wang, Bing Xiao, Yan Zheng, Xiao-Min Wang

Affiliation:

关键词: 阿尔茨海默病、ERK、JNK、p38、炎症、雷公藤内酯醇。

摘要: Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease characterized by aggregation of amyloid-β (Aβ) 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 Aβ 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 μg/kg) for 15 weeks markedly alleviated deficits in learning and memory, and prevented Aβ 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.

Cite this article as:

Yan-Qiu Cui, Qi Wang, Dong-Mei Zhang, Jun-Ya Wang, Bing Xiao, Yan Zheng, Xiao-Min Wang , Triptolide Rescues Spatial Memory Deficits and Amyloid-β Aggregation Accompanied by Inhibition of Inflammatory Responses and MAPKs Activity in APP/PS1 Transgenic Mice, Current Alzheimer Research 2016; 13 (3) . https://dx.doi.org/10.2174/156720501303160217122803