Open AccessDihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP 3 inflammasome activation in APP / PS 1 transgenic mice
Author(s) -
Feng Jie,
Wang JingXue,
Du YeHong,
Liu Ying,
Zhang Wei,
Chen JingFei,
Liu YuanJie,
Zheng Min,
Wang KeJian,
He GuiQiong
Publication year - 2018
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12983
Subject(s) - neuroinflammation , inflammasome , microglia , western blot , microbiology and biotechnology , chemistry , amyloid precursor protein , genetically modified mouse , pharmacology , biology , inflammation , transgene , alzheimer's disease , immunology , medicine , biochemistry , disease , gene
Summary Background Activated microglia‐mediated inflammation plays a key role in the pathogenesis of Alzheimer’s disease ( AD ). In addition, chronic activation of NLRP 3 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 / PS 1 transgenic mice. Methods After DHM was intraperitoneally injected in APP / PS 1 double‐transgenic mice, we assessed the effect of DHM on microglial activation, the expression of NLRP 3 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 ( BACE 1), 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 / PS 1 mice. In addition, APP / PS 1 mice show reduced activation of NLRP 3 inflammasomes and reduced expression of NLRP 3 inflammasome components. Furthermore, DHM could promote clearance of Aβ, a trigger for NLRP 3 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 NLRP 3 inflammasome‐based microglia‐mediated neuroinflammation and may be a promising therapeutic drug for treating AD .