5-HMF attenuates inflammation and demyelination in experimental autoimmune encephalomyelitis mice by inhibiting the
Dongsheng Guan1, Yingxia Li2, Yinglin Cui1
1Department of Neurology, the Second Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou 450002, China.
Abstract:
The neuroprotective role of 5-hydroxymethyl-2-furfural (5-HMF) has been demonstrated in a variety of neurological diseases. The aim of this study is to investigate the effect of 5-HMF on multiple sclerosis (MS). IFN-γ-stimulated murine microglia (BV2 cells) are considered a cell model of MS. With 5-HMF treatment, microglial M1/2 polarization and cytokine levels are detected. The interaction of 5-HMF with migration inhibitory factor (MIF) is predicted using online databases. The experimental autoimmune encephalomyelitis (EAE) mouse model is established, followed by a 5-HMF injection. The results show that 5-HMF facilitates IFN-γ-stimulated microglial M2 polarization and attenuates the inflammatory response. According to the network pharmacology and molecular docking results, 5-HMF has a binding site for MIF. Further results show that blocking MIF activity or silencing CD74 enhances microglial M2 polarization, reduces inflammatory activity, and prevents ERK1/2 phosphorylation. 5-HMF inhibits the MIF-CD74 interaction by binding to MIF, thereby inhibiting microglial M1 polarization and enhancing the anti-inflammatory response. 5-HMF ameliorates EAE, inflammation, and demyelination in vivo. In conclusion, our research indicates that 5-HMF promotes microglial M2 polarization by inhibiting the MIF-CD74 interaction, thereby attenuating inflammation and demyelination in EAE mice.
Insights
5-hydroxymethyl-2-furfural (5-HMF) shows neuroprotective effects in multiple sclerosis (MS) models. It promotes M2 microglial polarization and reduces inflammation by inhibiting the MIF-CD74 interaction, ameliorating disease symptoms.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Multiple sclerosis (MS) is a chronic neurological disease characterized by inflammation and demyelination.
- Microglial polarization plays a critical role in MS pathogenesis.
- 5-hydroxymethyl-2-furfural (5-HMF) has demonstrated neuroprotective properties in various neurological conditions.
Purpose of the Study:
- To investigate the therapeutic potential of 5-HMF in multiple sclerosis.
- To elucidate the underlying mechanisms of 5-HMF's action on microglial cells and inflammatory responses.
Main Methods:
- Utilized IFN-γ-stimulated murine microglia (BV2 cells) as an in vitro model for MS.
- Employed the experimental autoimmune encephalomyelitis (EAE) mouse model for in vivo studies.
- Performed network pharmacology and molecular docking to predict drug-target interactions.
- Assessed microglial polarization, cytokine levels, and inflammatory markers.
Main Results:
- 5-HMF treatment promoted M2 microglial polarization and attenuated inflammatory responses in vitro.
- Network pharmacology and molecular docking identified migration inhibitory factor (MIF) as a binding target for 5-HMF.
- Inhibition of MIF-CD74 interaction by 5-HMF enhanced M2 polarization and reduced inflammation.
- 5-HMF ameliorated EAE symptoms, inflammation, and demyelination in vivo.
Conclusions:
- 5-HMF exerts neuroprotective effects in MS by promoting microglial M2 polarization.
- The mechanism involves the inhibition of the MIF-CD74 interaction, leading to reduced inflammation and demyelination.
- 5-HMF represents a potential therapeutic agent for multiple sclerosis.
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