Eugenol relieves the pathological manifestations of Alzheimer's disease in 5×FAD mice

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid-β (Aβ) and excessive neuroinflammation, resulting in neuronal cell death and cognitive impairments. Eugenol, a phenylpropene, is the main component of Syzygium aromaticum L. (Myrtaceae) and has multiple therapeutic effects, including neuroprotective and anti-inflammatory effects, through multimodal mechanisms.We aimed to investigate the effect of eugenol on AD pathologies using a 5× familiar AD (5×FAD) mouse model.Eight-month-old 5×FAD and wild-type mice were administered with eugenol (10 or 30 mg/kg/day, p.o) for 2 months. Y-maze and Morris water maze tests were performed to assess the cognitive function of mice. After the behavioral test, molecular analysis was conducted to investigate the therapeutic mechanism of eugenol.Our findings indicate that eugenol treatment effectively mitigated cognitive impairments in 5×FAD mice. This beneficial effect was associated with a decrease in AD pathologies, including neuronal cell loss and Aβ deposition. Specifically, eugenol inhibited necroptosis activation and increased microglial phagocytosis, which were the underlying mechanisms for the observed reductions in neuronal cell loss and Aβ deposition, respectively.Overall, our data suggest that eugenol would be a potential therapeutic candidate for AD.