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Soluble Epoxide Hydrolase Inhibition Improves Alzheimer's Disease Hallmarks: Correlation with Peripheral Inflammation
Júlia Jarne-Ferrer1,2, Christian Griñán-Ferré1,2,3, Beatrice Jora4
1Department of Pharmacology, Toxicology and Therapeutic Chemistry, Universitat de Barcelona, 08028 Barcelona, Spain.
Aging and Disease
|May 27, 2025
Summary
Soluble epoxide hydrolase (sEH) inhibition with UB-BJ-02 modulated gut microbiota, reducing neuroinflammation and improving memory in Alzheimer
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- Neuroinflammation exacerbates neurodegenerative diseases, with gut microbiota implicated in its progression.
- Soluble epoxide hydrolase (sEH) is a novel therapeutic target for Alzheimer's Disease (AD).
Purpose of the Study:
- To investigate the neuroprotective effects of sEH inhibition via UB-BJ-02 in an AD mouse model.
- To explore the impact of UB-BJ-02 on gut microbiota composition and peripheral/central inflammatory markers.
Main Methods:
- Administered UB-BJ-02 to 5xFAD mice, a model for Alzheimer's Disease.
- Analyzed gut microbiota composition, peripheral cytokine production (e.g., Il-10), cognitive function, neuroinflammation markers (e.g., GFAP, IBA-1, Il-1β), Aβ plaque load, mitochondrial function, and protein levels (DRP1, OPA1).
- Validated findings in C. elegans by manipulating gut microbiota through feeding.
Main Results:
- UB-BJ-02 treatment shifted gut microbiota towards beneficial genera (Lactobacillus, Limosilactobacillus) and reduced pro-inflammatory ones (Bacteroides).
- Observed increased anti-inflammatory mediators (Il-10), improved memory, reduced neuroinflammation, decreased Aβ plaques, and enhanced mitochondrial function in treated mice.
- Demonstrated a correlation between UB-BJ-02's brain effects and gut microbiota changes, further supported by C. elegans experiments.
Conclusions:
- sEH inhibition with UB-BJ-02 exerts neuroprotective effects in an Alzheimer's Disease model.
- These effects are mediated through modulation of the gut microbiota, reduction of peripheral and central inflammation, and improvement of mitochondrial function.
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