Eugenitol ameliorates memory impairments in 5XFAD mice by reducing Aβ plaques and neuroinflammation

초록

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 beta (A beta) and anti-neuminflammatory effects, in an AD mouse model. We found that eugenitol potently inhibited A beta plaque and oligomer formation. Moreover, eugenitol dissociated the preformed A beta plaques and reduced A beta-induced nero2a cell death. An in silico docking simulation study showed that eugenitol may interact with A beta(1-42) 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 A beta 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 A beta deposits and neuminflammation in the hippocampus of 5XFAD mice. These results suggest that eugenitol, which has anti-A beta aggregation, A beta 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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