Eugenitol ameliorates memory impairments in 5XFAD mice by reducing Aβ plaques and neuroinflammation
Alzheimer’s disease (AD) is caused by various pathological mechanisms; therefore, it is necessary to develop drugs that simultaneously act on multiple targets. In this study, we investigated the effects of eugenitol, which has anti-amyloid β (Aβ) and anti-neuroinflammatory effects, in an AD mouse mo...
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Veröffentlicht in: | Biomedicine & pharmacotherapy 2022-04, Vol.148, p.112763, Article 112763 |
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Sprache: | eng |
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Zusammenfassung: | Alzheimer’s disease (AD) is caused by various pathological mechanisms; therefore, it is necessary to develop drugs that simultaneously act on multiple targets. In this study, we investigated the effects of eugenitol, which has anti-amyloid β (Aβ) and anti-neuroinflammatory effects, in an AD mouse model. We found that eugenitol potently inhibited Aβ plaque and oligomer formation. Moreover, eugenitol dissociated the preformed Aβ plaques and reduced Aβ-induced nero2a cell death. An in silico docking simulation study showed that eugenitol may interact with Aβ1–42 monomers and fibrils. Eugenitol showed radical scavenging effects and potently reduced the release of proinflammatory cytokines from lipopolysaccharide-treated BV2 cells. Systemic administration of eugenitol blocked Aβ aggregate-induced memory impairment in the Morris water maze test in a dose-dependent manner. In 5XFAD mice, prolonged administration of eugenitol ameliorated memory and hippocampal long-term potentiation impairment. Moreover, eugenitol significantly reduced Aβ deposits and neuroinflammation in the hippocampus of 5XFAD mice. These results suggest that eugenitol, which has anti-Aβ aggregation, Aβ fibril dissociation, and anti-inflammatory effects, potently modulates AD-like pathologies in 5XFAD mice, and could be a promising candidate for AD therapy.
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ISSN: | 0753-3322 1950-6007 |
DOI: | 10.1016/j.biopha.2022.112763 |