Matrine protects against experimental autoimmune encephalomyelitis through modulating microglial ferroptosis

Multiple sclerosis (MS) is an inflammatory demyelination neurodegenerative disease of the central nervous system (CNS). Ferroptosis has been implicated in a range of brain disorders, and iron-loaded microglia are frequently found in affected brain regions. However, the molecular mechanisms linking f...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2024-11, Vol.735, p.150651, Article 150651
Main Authors: Feng, Furui, Li, Xinyu, Wang, Wenbin, Dou, Mengmeng, Li, Silu, Jin, Xin, Chu, Yaojuan, Zhu, Lin
Format: Article
Language:English
Subjects:
EAE
Ferroptosis
Inflammation
Matrine
Oxidative stress
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multiple sclerosis (MS) is an inflammatory demyelination neurodegenerative disease of the central nervous system (CNS). Ferroptosis has been implicated in a range of brain disorders, and iron-loaded microglia are frequently found in affected brain regions. However, the molecular mechanisms linking ferroptosis with MS have not been well-defined. The present study seeks to bridge this gap and investigate the impact of matrine (MAT), a herbal medicine with immunomodulatory capacities, on the regulation of oxidative stress and ferroptosis in the CNS of mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. CNS of EAE mice contained elevated levels of ferroptosis-related molecules, e.g., MDA, LPCAT3 and PTGS2, but decreased expression of antioxidant molecules, including GSH and SOD, GPX4 and SLC7A11. This pathogenic process was reversed by MAT treatment, together with significant reduction of disease severity and CNS inflammatory demyelination. Furthermore, the expression of PTGS2 and LOX was largely increased in microglia of EAE mice, accompanied with increased production of IL-6 and TNF-α, indicating a proinflammatory phenotype of microglia that undergo oxidative stress/ferroptosis, and their expression was significantly reduced after MAT treatment. Together, our results indicate that ferroptosis/inflammation plays an important role in the pathogenesis of CNS autoimmunity, and inhibiting ferroptosis-induced microglial activation/inflammation could be a novel mechanism underlying the therapeutic effects of MAT on CNS inflammatory demyelination in EAE. •Multiple indicators of ferroptosis have been validated to occur in the EAE model, providing a basis for potential therapeutic targets for multiple sclerosis.•Matrine repairs the SLC7A11-GPX4 axis damage induced by the EAE model.•Matrine mitigated oxidative stress and attenuated inflammation in an EAE model.•Matrine can inhibit lipid peroxidation and protect microglia from ferroptosis in EAE model.
ISSN:0006-291X
1090-2104
1090-2104
DOI:10.1016/j.bbrc.2024.150651