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Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice.
CNS Neurosci Ther. 2018 12; 24(12):1207-1218.CN

Abstract

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.

Authors+Show Affiliations

Institute of Neuroscience, Chongqing Medical University, Chongqing, China.Institute of Immunology, Third Military Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China. Department of Anatomy, Chongqing Medical University, Chongqing, China.School of Medicine, University of Electronic Science and Technology, Chengdu, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China. Department of Anatomy, Chongqing Medical University, Chongqing, China.Institute of Neuroscience, Chongqing Medical University, Chongqing, China. Department of Anatomy, Chongqing Medical University, Chongqing, China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29869390

Citation

Feng, Jie, et al. "Dihydromyricetin Inhibits Microglial Activation and Neuroinflammation By Suppressing NLRP3 Inflammasome Activation in APP/PS1 Transgenic Mice." CNS Neuroscience & Therapeutics, vol. 24, no. 12, 2018, pp. 1207-1218.
Feng J, Wang JX, Du YH, et al. Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice. CNS Neurosci Ther. 2018;24(12):1207-1218.
Feng, J., Wang, J. X., Du, Y. H., Liu, Y., Zhang, W., Chen, J. F., Liu, Y. J., Zheng, M., Wang, K. J., & He, G. Q. (2018). Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice. CNS Neuroscience & Therapeutics, 24(12), 1207-1218. https://doi.org/10.1111/cns.12983
Feng J, et al. Dihydromyricetin Inhibits Microglial Activation and Neuroinflammation By Suppressing NLRP3 Inflammasome Activation in APP/PS1 Transgenic Mice. CNS Neurosci Ther. 2018;24(12):1207-1218. PubMed PMID: 29869390.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice. AU - Feng,Jie, AU - Wang,Jing-Xue, AU - Du,Ye-Hong, AU - Liu,Ying, AU - Zhang,Wei, AU - Chen,Jing-Fei, AU - Liu,Yuan-Jie, AU - Zheng,Min, AU - Wang,Ke-Jian, AU - He,Gui-Qiong, Y1 - 2018/06/04/ PY - 2017/10/18/received PY - 2018/03/28/revised PY - 2018/04/30/accepted PY - 2018/6/6/pubmed PY - 2019/10/15/medline PY - 2018/6/6/entrez KW - Alzheimer’s disease KW - NLRP3 inflammasome KW - dihydromyricetin KW - microglia SP - 1207 EP - 1218 JF - CNS neuroscience & therapeutics JO - CNS Neurosci Ther VL - 24 IS - 12 N2 - 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. SN - 1755-5949 UR - https://www.unboundmedicine.com/medline/citation/29869390/Dihydromyricetin_inhibits_microglial_activation_and_neuroinflammation_by_suppressing_NLRP3_inflammasome_activation_in_APP/PS1_transgenic_mice_ L2 - https://doi.org/10.1111/cns.12983 DB - PRIME DP - Unbound Medicine ER -