Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice.
Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice.
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二氢杨梅素通过抑制 APP/PS1 转基因小鼠的 NLRP3 炎症小体激活来抑制小胶质细胞激活和神经炎症
DOI：
10.1111/cns.12983
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发表时间：
2018-12
影响因子：
5.5
通讯作者：
He GQ
中科院分区：
文献类型：
--
作者：
Feng J;Wang JX;Du YH;Liu Y;Zhang W;Chen JF;Liu YJ;Zheng M;Wang KJ;He GQ
活化的小胶质细胞介导的炎症在阿尔茨海默病（AD）的发病机制中起关键作用。此外，由小胶质细胞中的淀粉样β肽（Aβ）触发的NLRP 3炎性体的慢性激活有助于持续的神经炎症。在这里，主要目标是评估二氢杨梅素（DHM），一种植物类黄酮化合物，是否是AD的有效疗法;关键是要知道DHM是否会影响APP/PS1转基因小鼠中的小胶质细胞活化和神经炎症。在APP/PS1双转基因小鼠中腹腔注射DHM后，我们通过免疫荧光和Western blot评估了DHM对小胶质细胞活化，NLRP 3炎性体组分表达以及炎性细胞因子IL-1β产生的影响。为了确定DHM是否在Aβ产生和沉积中起作用，通过Western blot检测淀粉样β蛋白前体（APP）和β位点APP裂解酶1（BACE 1）以及脑啡肽酶（NEP）。最后，通过Morris水迷宫测试行为，以说明DHM治疗是否具有改善AD记忆和认知缺陷的显著积极作用。二氢杨梅素治疗显著改善记忆和认知缺陷，减少APP/PS1小鼠海马和皮质中活化小胶质细胞的数量。此外，APP/PS1小鼠显示NLRP 3炎性体的活化减少和NLRP 3炎性体组分的表达减少。此外，DHM可通过增加NEP水平促进Aβ（NLRP 3炎性小体激活的触发因素）的清除，并将小胶质细胞转化为M2特异性聚集酶-1阳性细胞表型，这可增强小胶质细胞对Aβ及其聚集体的清除，但不产生Aβ。总之，我们的研究结果表明，DHM通过抑制基于NLRP 3炎性小体的小胶质细胞介导的神经炎症来预防AD样病理的进展，并且可能是治疗AD的有希望的治疗药物。
Activated microglia‐mediated inflammation plays a key role in the pathogenesis of Alzheimer’s disease (AD). In addition, chronic activation of NLRP3 inflammasomes triggered by amyloid β peptide (Aβ) in microglia contributes to persistent neuroinflammation. Here, the primary goal was to assess whether Dihydromyricetin (DHM), a plant flavonoid compound, is effective therapies for AD; it is crucial to know whether DHM will affect microglial activation and neuroinflammation in APP/PS1 transgenic mice. After DHM was intraperitoneally injected in APP/PS1 double‐transgenic mice, we assessed the effect of DHM on microglial activation, the expression of NLRP3 inflammasome components, and the production of inflammatory cytokine IL‐1β by immunofluorescence and Western blot. To determine whether DHM play roles in the Aβ production and deposition, amyloid β protein precursor (APP) and β‐site APP cleaving enzyme1 (BACE1), as well as neprilysin (NEP), were detected by Western blot. Finally, behavior was tested by Morris Water Maze to illustrate whether DHM treatment has a significantly positive effect on ameliorating the memory and cognition deficits in AD. Dihydromyricetin treatment significantly ameliorated memory and cognition deficits and decreased the number of activated microglia in the hippocampus and cortex of APP/PS1 mice. In addition, APP/PS1 mice show reduced activation of NLRP3 inflammasomes and reduced expression of NLRP3 inflammasome components. Furthermore, DHM could promote clearance of Aβ, a trigger for NLRP3 inflammasome activation, by increasing levels of NEP and shift microglial conversion to the M2‐specific agrinase‐1‐positive cell phenotype, which enhances microglial clearance of Aβ and its aggregates but not production of Aβ. Taken together, our findings suggest that DHM prevents progression of AD‐like pathology through inhibition of NLRP3 inflammasome‐based microglia‐mediated neuroinflammation and may be a promising therapeutic drug for treating AD.
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DOI：
10.1155/2017/1053617
发表时间：
2017
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Li H;Li Q;Liu Z;Yang K;Chen Z;Cheng Q;Wu L
通讯作者：
Wu L
影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.1
作者：
Lue, Lih-Fen;Kuo, Yu-Min;Beach, Thomas;Walker, Douglas G.
通讯作者：
Walker, Douglas G.
影响因子：
15.1
作者：
Saresella M;La Rosa F;Piancone F;Zoppis M;Marventano I;Calabrese E;Rainone V;Nemni R;Mancuso R;Clerici M
通讯作者：
Clerici M