Neuroprotective effects of astragaloside IV on Parkinson disease models of mice and primary astrocytes

Xia, Lei; Guo, De‐An; Chen, Bing

doi:10.3892/etm.2017.5238

Cited by 16 publications

(16 citation statements)

References 36 publications

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“…Many studies have demonstrated that AS-IV possesses neuroprotective effects that can reverse or alleviate various central nervous system diseases, such as Parkinson's disease and cerebral ischaemia. 21,22 In the present study, we provide evidence that AS-IV rendered a beneficial effect on neuroprotection against SCI. We found that (a) AS-IV promotes autophagy and inhibits neuronal apoptosis after SCI.…”

Section: Discussionsupporting

confidence: 62%

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Lin

Pan

Huang

et al. 2019

J Cellular Molecular Medi

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Inflammation and neuronal apoptosis contribute to the progression of secondary injury after spinal cord injury (SCI) and are targets for SCI therapy; autophagy is reported to suppress apoptosis in neuronal cells and M2 polarization may attenuate inflammatory response in microglia, while both are negatively regulated by mTORC1 signalling. We hypothesize that mTORC1 suppression may have dual effects on inflammation and neuronal apoptosis and may be a feasible approach for SCI therapy. In this study, we evaluate a novel inhibitor of mTORC1 signalling, Astragaloside IV (AS‐IV), in vitro and in vivo. Our results showed that AS‐IV may suppress mTORC1 signalling both in neuronal cells and microglial cells in vitro and in vivo. AS‐IV treatment may stimulate autophagy in neuronal cells and protect them against apoptosis through autophagy regulation; it may also promote M2 polarization in microglial cells and attenuate neuroinflammation. In vivo, rats were intraperitoneally injected with AS‐IV (10 mg/kg/d) after SCI, behavioural and histological evaluations showed that AS‐IV may promote functional recovery in rats after SCI. We propose that mTORC1 suppression may attenuate both microglial inflammatory response and neuronal apoptosis and promote functional recovery after SCI, while AS‐IV may become a novel therapeutic medicine for SCI.

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Section: Discussionsupporting

confidence: 62%

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Lin

Pan

Huang

et al. 2019

J Cellular Molecular Medi

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“…The 6-OHDA-treated SH-SY5Y cells were incubated with diverse concentrations of AS-IV (25, 50, and 100 μM), and it was found that AS-IV dose-dependently enhanced cell viability and repaired morphological damages. AS-IV is also demonstrated to rescue MPP + -induced cell viability reduction in vitro , implying that AS-IV may act as a promising neuroprotective agent for PD ( Xia et al, 2017 ). PD is featured by degeneration of dopaminergic neurons in substantia nigra striatum circuit, which is bound up with subsequent chronic neuroinflammation ( Wei et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

Xu¹,

Yang²,

Huang³

et al. 2021

Front. Neurosci.

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ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson’s disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and MethodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25–100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

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“…AST-IV has been reported to exert anti-inflammatory and neuroprotective effects in various disease models [21,31]. AST-IV-induced anti-inflammatory effects indicate its potential application in the treatment of neuroinflammatory and neurodegenerative diseases [12,34]. AST-IV can attenuate the H 2 O 2 -induced apoptosis of neuronal cells and exert protective effects against neurodegenerative diseases via the p38 MAPK pathway, and attenuate glutamate-induced neurotoxicity in PC12 cells through Raf-MEK-ERK pathway [24,37].…”

Section: Discussionmentioning

confidence: 99%

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

Yu¹,

Guo²,

Lǐ³

et al. 2019

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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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Neuroprotective effects of astragaloside IV on Parkinson disease models of mice and primary astrocytes

Cited by 16 publications

References 36 publications

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Dual regulation of microglia and neurons by Astragaloside IV‐mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury

Astragaloside IV Protects 6-Hydroxydopamine-Induced SH-SY5Y Cell Model of Parkinson’s Disease via Activating the JAK2/STAT3 Pathway

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

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