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Folia Neuropathologica
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2/2019
vol. 57
 
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abstract:
Original paper

Astragaloside IV protects neurons from microglia-mediated cell damage through promoting microglia polarization

Jingwen Yu
1
,
Minfang Guo
1
,
Yanhua Li
1
,
Huiyu Zhang
1
,
Zhi Chai
2
,
Qing Wang
2
,
Yuqing Yan
1
,
Jiezhong Yu
1
,
Chunyun Liu
1
,
Guangxian Zhang
1, 3
,
Ma Cungen
1

1.
Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, China
2.
Shanxi University of Chinese Medicine, Jinzhong, China
3.
Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA
Folia Neuropathol 2019; 57 (2):170-181
DOI: https://doi.org/10.5114/fn.2019.86299
Online publish date: 2019/06/28
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Astragaloside IV (AST-IV) is a major active ingredient of astragalus, with a neuroprotective effect. The current study is aimed to investigate the impact of AST-IV on the M1/M2 microglial activation in response to lipopolysaccharide (LPS) stimulation, how AST-IV attenuated microglia-mediated neuronal damage, and the molecular mechanisms underlying AST-IV’s protection of neurons against microglia-mediated neuronal damage. Our results showed that AST-IV partially protected microglia from death evoked by LPS and downregulated the release of pro-inflammatory (M1) mediators including interleukin (IL)-1β, IL-6, tumour necrosis factor α (TNF-α) and nitric oxide, as well as the expression of Toll-like receptors 4 (TLR4), MyD88, and nuclear factor κB (NF-κB) of these cells. In contrast, AST-IV elevated the production of anti-inflammatory cytokine IL-10 and expression of arginase 1, an M2 marker of microglia, whose conditioned medium promoted PC12 neurons survival. These results indicate that AST-IV exerts an anti-inflammatory effect on microglia, possibly through inhibiting TLR4/NF-κB signalling pathways, and protects neurons from microglia-mediated cell death through conversion of microglia from inflammatory M1 to an anti-inflammatory M2 phenotype.
keywords:

astragaloside IV, neuroinflammatory, neurons, microglia polarization, TLR4 intracellular pathways
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