Folia Neuropathologica (Jun 2019)

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

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

DOI
https://doi.org/10.5114/fn.2019.86299
Journal volume & issue
Vol. 57, no. 2
pp. 170 – 181

Abstract

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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.

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