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

Abstract

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.

Astragaloside IV Ameliorates Cognitive Impairment and Neuroinflammation in an Oligomeric Aβ Induced Alzheimer’s Disease Mouse Model <i>via</i> Inhibition of Microglial Activation and NADPH Oxidase Expression

“…In LPS induced BV2 and primary microglia cells, AS-IV could significantly reduce the release of inflammatory mediators through activating NRF2/HO-1 via ERK signaling pathway 34) . In a report investigating the effect of AS-IV on the microglia activation stimulated by LPS, AS-IV was found to exert anti-inflammatory effect through inhibiting TLR4/NF-κB pathway and converting microglia from inflammatory M1 phenotype to anti-inflammatory M2 phenotype 35) . Moreover, it was reported that AS-IV inhibits microglial activation partially by activating glucocorticoid receptor mediated signaling pathway 36) .…”

The Emerging Role of Central and Peripheral Immune Systems in Neurodegenerative Diseases

“…It also modulates ERK and NF-κB pathways, decreases levels of proinflammatory cytokines in the brain and reduces neuroinflammation (Lin et al, 2019 ). Astragaloside IV (AST-IV) can exert anti-inflammatory effects on microglia by inhibiting the TLR4/NF-κB signaling pathway and promote the transformation of microglia to a neuroprotective M2 phenotype (Yu et al, 2019 ). In addition, QMAD, a dichloromethane soluble fraction of the Chinese herb QuMai, induces Tregs by altering intracellular signaling that restricts AKT phosphorylation (Reid-Adam et al, 2013 ), which may be a new strategy for the treatment of ALS.…”

Current Progress on Neuroprotection Induced by Artemisia, Ginseng, Astragalus, and Ginkgo Traditional Chinese Medicines for the Therapy of Alzheimer’s Disease

“…Panax ginseng extract and ginsenoside Rg1 significantly suppressed the signaling transduction pathway of TLR3 and TLR4 and decreased the inflammation factors induced by A β 25-35 in neuroglial NG108-15 cell culture [ 222 ]. Astragaloside IV exerted anti-inflammatory effects on microglia by inhibiting TLR4/NF- κ B signaling pathways and protected neurons from microglia-mediated cell death through microglia polarization [ 223 ]. Ginkgo diterpene lactones alleviated LPS-induced inflammatory response in primary astrocytes by downregulation of the TLR4/NF- κ B signal pathway [ 224 ], and ginkgolide B alleviated learning and memory impairment in rats with vascular dementia by reducing neuroinflammation due to decreased activity of the TLR4/NF- κ B pathway [ 225 ].…”