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The Matrine Derivative MASM Alleviates LPS-Induced Depressive-Like Behavior in Mice by Modulating Hippocampal
Chao-Ran Li1, Zhang-Yang Xu1, Lu-Na Sun1
1Department of Nautical Psychology, Faculty of Psychology, Naval Medical University, 200433 Shanghai, China.
Alpha Psychiatry
|November 10, 2025
Summary
This study shows that (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diaza-benzo(de)anthracene-8-thione (MASM) can reduce depression-like behaviors and neuroinflammation. MASM works by decreasing oxidative stress and enhancing autophagy.
Area of Science:
- Neuroscience
- Pharmacology
- Immunology
Background:
- Neuroinflammation is linked to major depressive disorder (MDD).
- (6aS,10S,11aR,11bR,11cS)-10-methylamino-dodecahydro-3a,7a-diaza-benzo(de)anthracene-8-thione (MASM), a matrine derivative, exhibits anti-inflammatory effects.
- The impact of MASM on lipopolysaccharide (LPS)-induced depression and its mechanisms are not well understood.
Purpose of the Study:
- To evaluate the efficacy of MASM in mitigating LPS-induced depressive behaviors.
- To investigate the underlying molecular mechanisms of MASM's action in a neuroinflammation model.
Main Methods:
- Depressive behaviors were assessed in LPS-treated mice using forced swim and tail suspension tests.
- BV2 microglial cells were used to model LPS-induced neuroinflammation.
- ELISA, immunoblotting, and flow cytometry were employed to measure inflammatory markers, oxidative stress, and autophagy-related proteins.
Main Results:
- MASM significantly reduced depressive-like behaviors in LPS-treated mice.
- MASM downregulated pro-inflammatory cytokines (TNF-α, HMGB1) and oxidative stress markers (ROS).
- MASM upregulated neuroprotective proteins (HO-1, SIRT-1) and restored autophagic flux (LC3-II/p62 ratio).
Conclusions:
- MASM demonstrates potential as a therapeutic agent for depression associated with neuroinflammation.
- MASM alleviates LPS-induced neuroinflammation and depressive behaviors by reducing oxidative stress and promoting autophagy.
