Alzheimer’s disease (AD) presents a growing societal challenge, driven by an aging population. It is characterized by neurodegeneration linked to β-amyloid (Aβ) and tau protein aggregation. Reactive glial cell–mediated neuroinflammation exacerbates disease progression by facilitating the accumulation of Aβ and impairing its clearance, thus highlighting potential therapeutic targets. Aerial parts of Artemisia iwayomogi (AIH), a kind of mugwort, has been consumed as a medicinal herb in East Asia for relieving inflammation-related diseases. Previously, AIH was found to exert potent inhibitory effects on neuroinflammation. This study aimed to examine whether AIH mitigates AD pathogenesis by regulating neuroinflammation and reducing Aβ deposition. AIH treatment to primary mixed glial cultures attenuated the pro-inflammatory responses evoked by Aβ stimulation. When treated to 5 × familial AD (5xFAD) mice, AIH improved learning and cognitive ability and reduced Aβ burden in the brain. AIH suppressed glial overactivation, as well as inhibited the expressions of pro-inflammatory mediators in the brain. Moreover, AIH regulated AKT signaling and elevated the expression of autophagy-lysosomal mediators in vitro. It was confirmed that lysosome-associated membrane protein 1 (LAMP1) was increased in the Aβ-associated microglia in the mouse hippocampus. Finally, it was observed that tau phosphorylation was alleviated, and synaptic protein expression was increased in AIH-treated 5xFAD mice. Overall, this study demonstrated that AIH ameliorated excessive neuroinflammation and Aβ accumulation by regulating microglial activation and autophagy-lysosomal pathway, thereby suggesting AIH as a promising therapeutic candidate for AD treatment.

阿尔茨海默病 （AD） 在人口老龄化的推动下，带来了日益严峻的社会挑战。它的特征是与 β-淀粉样蛋白 （Aβ） 和 tau 蛋白聚集相关的神经退行性变。反应性神经胶质细胞介导的神经炎症通过促进 Aβ 的积累并损害其清除来加剧疾病进展，从而突出潜在的治疗靶点。艾蒿 （AIH） 是一种艾蒿，其地上部分在东亚被用作药草，用于缓解炎症相关疾病。以前，发现 AIH 对神经炎症具有有效的抑制作用。本研究旨在检查 AIH 是否通过调节神经炎症和减少 Aβ 沉积来减轻 AD 发病机制。原代混合胶质细胞培养物的 AIH 治疗减弱了 Aβ 刺激诱发的促炎反应。当对 5 × 家族性 AD （5xFAD） 小鼠进行治疗时，AIH 改善了学习和认知能力，并减轻了大脑中的 Aβ 负担。AIH 抑制神经胶质细胞过度激活，并抑制大脑中促炎介质的表达。此外，AIH 在体外调节 AKT 信号传导并升高自噬-溶酶体介质的表达。证实溶酶体相关膜蛋白 1 （LAMP1） 在小鼠海马 Aβ 相关小胶质细胞中增加。最后，观察到 AIH 处理的 5xFAD 小鼠的 tau 磷酸化减轻，突触蛋白表达增加。总体而言，本研究证明 AIH 通过调节小胶质细胞活化和自噬-溶酶体途径改善过度的神经炎症和 Aβ 积累，从而表明 AIH 是 AD 治疗的有前途的治疗候选者。