Department of Fundamental Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Phytomedicine. 2023 Sep;118:154930. doi: 10.1016/j.phymed.2023.154930. Epub 2023 Jun 14.
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.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是淀粉样蛋白-β（Aβ）的积累和过度神经炎症，导致神经元细胞死亡和认知障碍。丁香酚是一种苯丙烯，是丁子香属（桃金娘科）的主要成分，具有多种治疗作用，包括神经保护和抗炎作用，通过多模式机制。
我们旨在使用 5×熟悉 AD（5×FAD）小鼠模型研究丁香酚对 AD 病理的影响。
给予 8 月龄 5×FAD 和野生型小鼠丁香酚（10 或 30mg/kg/天，口服）2 个月。进行 Y 迷宫和 Morris 水迷宫测试以评估小鼠的认知功能。行为测试后，进行分子分析以研究丁香酚的治疗机制。
我们的研究结果表明，丁香酚治疗可有效减轻 5×FAD 小鼠的认知障碍。这种有益的作用与 AD 病理的减少有关，包括神经元细胞丢失和 Aβ沉积。具体而言，丁香酚抑制坏死性凋亡的激活并增加小胶质细胞的吞噬作用，这分别是观察到的神经元细胞丢失和 Aβ沉积减少的潜在机制。
总体而言，我们的数据表明丁香酚可能是 AD 的潜在治疗候选药物。
