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Updated: Dec 7, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
The anti-STAT1 polyphenol myricetin inhibits M1 microglia activation and counteracts neuronal death
Diana Boriero1, Alessandra Carcereri de Prati1, Lorenzo Antonini2
1Neurosciences, Biomedicine and Movement Sciences, Biological Chemistry Section, University of Verona, Verona, Italy.
Abstract:
Microglia activation toward M1 pro-inflammatory phenotype represents one of the earliest events of neurological disorders. Therefore, reducing microglia activation should inhibit neuroinflammation, thereby delaying the progression of neurodegeneration. Recently, we pointed out the role of STAT1 signaling in hypoxia-induced M1 activation and proposed STAT1 as a suitable molecular target for the prevention and treatment of neurodegeneration. Myricetin (MYR) is a natural flavonoid that exhibits a specific anti-STAT1 activity correlated with its direct interaction with STAT1 protein itself. Herein, we investigated the anti-inflammatory effect of MYR and its ability to protect neurons from death in an in vitro model of neurotoxicity using the neuroblast-like SH-SY5Y cells that were exposed to conditioned media from hypoxia-activated microglia BV2 cells. We demonstrate that MYR pretreatment is able to switch off hypoxia-induced M1 microglia polarization through the inhibition of STAT1 signaling. The analysis of the molecular mechanism suggests that the direct interaction of MYR with STAT1 impairs its S-glutathionylation and phosphorylation. Moreover, treatment of SH-SY5Y cells with conditioned medium from hypoxia-activated microglia pretreated with MYR produced a significant reduction in neuronal viability. Our data indicate that MYR may represent a promising candidate for prevention and treatment of neuroinflammation in neurodegenerative disorders.
Insights
Myricetin (MYR) reduces neuroinflammation by inhibiting STAT1 signaling in activated microglia, protecting neurons from death. This natural flavonoid shows promise for treating neurodegenerative disorders.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglia activation to a pro-inflammatory M1 phenotype is an early event in neurological disorders.
- STAT1 signaling plays a crucial role in hypoxia-induced M1 microglia activation, making it a potential therapeutic target.
- Myricetin (MYR), a natural flavonoid, has demonstrated anti-STAT1 activity through direct protein interaction.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Myricetin (MYR).
- To evaluate MYR's ability to protect neurons from death in an in vitro neurotoxicity model.
- To explore MYR's mechanism of action in modulating microglia activation and neuroinflammation.
Main Methods:
- Utilized an in vitro model with neuroblast-like SH-SY5Y cells exposed to conditioned media from hypoxia-activated BV2 microglia.
- Pretreated microglia with MYR to assess its impact on M1 polarization and STAT1 signaling.
- Analyzed MYR's interaction with STAT1, including its effects on S-glutathionylation and phosphorylation.
- Assessed neuronal viability after exposure to conditioned media from MYR-treated microglia.
Main Results:
- MYR pretreatment effectively inhibited hypoxia-induced M1 microglia polarization by suppressing STAT1 signaling.
- MYR's direct interaction with STAT1 impaired its S-glutathionylation and phosphorylation.
- Conditioned media from MYR-pretreated microglia significantly reduced neuronal death in SH-SY5Y cells.
Conclusions:
- MYR demonstrates significant anti-inflammatory effects by modulating microglia activation via STAT1 inhibition.
- MYR offers neuroprotection by reducing the toxicity of activated microglia.
- Myricetin is a promising therapeutic candidate for preventing and treating neuroinflammation in neurodegenerative diseases.
