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Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice
BACKGROUND: 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 a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282966/ https://www.ncbi.nlm.nih.gov/pubmed/29869390 http://dx.doi.org/10.1111/cns.12983 |
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author | Feng, Jie Wang, Jing‐Xue Du, Ye‐Hong Liu, Ying Zhang, Wei Chen, Jing‐Fei Liu, Yuan‐Jie Zheng, Min Wang, Ke‐Jian He, Gui‐Qiong |
author_facet | Feng, Jie Wang, Jing‐Xue Du, Ye‐Hong Liu, Ying Zhang, Wei Chen, Jing‐Fei Liu, Yuan‐Jie Zheng, Min Wang, Ke‐Jian He, Gui‐Qiong |
author_sort | Feng, Jie |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. |
format | Online Article Text |
id | pubmed-6282966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62829662018-12-14 Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice Feng, Jie Wang, Jing‐Xue Du, Ye‐Hong Liu, Ying Zhang, Wei Chen, Jing‐Fei Liu, Yuan‐Jie Zheng, Min Wang, Ke‐Jian He, Gui‐Qiong CNS Neurosci Ther Original Articles BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. John Wiley and Sons Inc. 2018-06-04 /pmc/articles/PMC6282966/ /pubmed/29869390 http://dx.doi.org/10.1111/cns.12983 Text en © 2018 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Feng, Jie Wang, Jing‐Xue Du, Ye‐Hong Liu, Ying Zhang, Wei Chen, Jing‐Fei Liu, Yuan‐Jie Zheng, Min Wang, Ke‐Jian He, Gui‐Qiong Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title | Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title_full | Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title_fullStr | Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title_full_unstemmed | Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title_short | Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice |
title_sort | dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing nlrp3 inflammasome activation in app/ps1 transgenic mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282966/ https://www.ncbi.nlm.nih.gov/pubmed/29869390 http://dx.doi.org/10.1111/cns.12983 |
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