Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive memory loss. Magnolol (MN), the main active ingredient of Magnolia officinalis, possesses anti-AD effects in several experimental models of AD. In this study, we aimed to explore whether MN could ameliorate the cognitive deficits in TgCRND8 transgenic mice and to elucidate its molecular mechanisms. Male TgCRND8 mice were orally administered with MN (20 and 40 mg/kg) daily for 4 consecutive months, followed by assessing the spatial learning and memory functions using the open-field, radial arm maze, and novel object recognition tests. The results demonstrated that MN (20 and 40 mg/kg) could markedly ameliorate the cognitive deficits in TgCRND8 mice. In addition, MN significantly increased the expression of postsynaptic density protein 93 (PSD93), PSD-95, synapsin-1, synaptotagmin-1, synaptophysin (SYN), and interleukin-10 (IL-10), while markedly reduced the protein levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-1β, Aβ₄₀, and Aβ₄₂, and modulated the amyloid precursor protein (APP) processing and phosphorylation. Immunofluorescence showed that MN significantly suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the hippocampus and cerebral cortex of TgCRND8 mice. Mechanistic studies revealed that MN could significantly increase the ratios of p-GSK-3β (Ser9)/GSK-3β, p-Akt (Ser473)/Akt, and p-NF-κB p65/NF-κB p65. These findings indicate that MN exerted cognitive deficits improving effects via suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction through regulating the PI3K/Akt/GSK-3β and NF-κB pathways, suggesting that MN is a promising naturally occurring polyphenol worthy of further developing into a therapeutic agent for AD treatment.

中文翻译：

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厚朴酚改善阿尔茨海默氏病转基因小鼠模型中的行为障碍和神经病理学。

阿尔茨海默氏病（AD）是一种常见的神经退行性疾病，其特征是进行性记忆丧失。厚朴酚（MN），主要活性成分厚朴在多种AD实验模型中均具有抗AD作用。在这项研究中，我们旨在探讨MN是否可以缓解TgCRND8转基因小鼠的认知缺陷，并阐明其分子机制。每天对雄性TgCRND8小鼠口服MN（20和40 mg / kg），连续4个月，然后使用开放视野，arm臂迷宫和新颖的物体识别测试评估空间学习和记忆功能。结果表明，MN（20和40 mg / kg）可以明显改善TgCRND8小鼠的认知功能障碍。此外，MN显着增加了突触后密度蛋白93（PSD93），PSD-95，synapsin-1，synaptotagmin-1，synaptophysin（SYN）和白细胞介素10（IL-10）的表达，同时显着降低了蛋白水平坏死因子α（TNF-α），IL-6，IL-1 β，A β ₄₀和A β ₄₂，和调制的淀粉样前体蛋白（APP）的处理和磷酸化。免疫荧光显示，MN显着抑制TgCRND8小鼠海马和大脑皮层小胶质细胞（Iba-1）和星形胶质细胞（GFAP）的激活。机制研究揭示，MN可以显著增加对GSK-3的比率β（Ser9）/ GSK-3 β，磷酸化Akt（Ser473上）/ Akt信号，和对NF- κ乙P65 / NF- κB p65。这些结果表明，MN通过调节PI3K / AKT / GSK-3施加的认知缺陷改善通过抑制神经炎症，淀粉样蛋白病理学和突触功能障碍的效果β和NF- κ乙途径，这表明MN是值得的另一个有前途的天然存在的多酚发展成为用于AD治疗的治疗剂。