Ellagic acid(EA) ameliorates Alzheimer's disease by reducing Aβ levels, oxidative stress and attenuating inflammation.

Abstract

Background: Ellagic acid (EA) serves as a pivotal coenzyme for various dehydrogenases, influencing diverse biological processes. Recognized for its potential in impeding disease progression, EA's effectiveness and mechanism in treating 5xFAD remain elusive.

Aim of the study: This study aims to investigate EA's potential roles and underlying mechanisms in mitigating symptoms associated with 5xFAD.

Materials and methods: 5 × FAD mice underwent a 12-week EA treatment regimen. The efficacy of EA against 5 × FAD was assessed through in vivo experiments, including Morris water maze and contextual fear conditioning tests for learning and memory abilities. Immunofluorescence (IF) and thioflavin staining examined changes in Aβ/neurons in brain tissue. RT‒qPCR evaluated inflammatory cytokine expression, while Bcl2/Bax protein levels were analyzed via Western blot (WB).

Results: EA demonstrates promise in alleviating symptoms associated with 5xFAD. It significantly reduced the mice's escape latency in the Morris water maze, increased the frequency of crossings in the target quadrant, and prolonged freezing time in the contextual fear memory test. EA also improved neuronal pathology in the hippocampus and cortex, decreased neuronal loss, and reduced Aβ levels. Moreover, EA significantly increased MDA and SOD levels, effectively modulated the Bcl2/Bax ratio, and decreased the production of proinflammatory factors in brain tissue of 5xFAD model mice.

In conclusion: Our findings highlight the potential therapeutic efficacy of EA in addressing 5xFAD-related nervous system disorders by targeting Aβ levels, oxidative stress, and inflammation.