Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology of Guizhou Province, Key Laboratory of Molecular Biology of Guizhou Medical University, Guiyang, China.
Guiyang Healthcare Vocational University, Guizhou ERC for Medical Resources & Healthcare Products (Guizhou Engineering Research Center for Medical Resources and Healthcare Products), Guiyang, Guizhou, China.
Biomed Pharmacother. 2024 Aug;177:116963. doi: 10.1016/j.biopha.2024.116963. Epub 2024 Jun 17.
Alzheimer's disease is characterized by abnormal β-amyloid (Aβ) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin.
The effect of myricetin was assessed on Aβ oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3β (GSK3β) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress.
We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aβ oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3β and ERK 2 signalling pathways.
This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer's disease.
阿尔茨海默病的特征是异常β-淀粉样蛋白（Aβ）斑块积累、tau 过度磷酸化、反应性氧化应激、线粒体功能障碍和突触丧失。杨梅素是一种膳食类黄酮，已被证明具有体外和体内的神经保护作用。在这里，我们旨在阐明杨梅素保护作用涉及的机制和途径。
评估杨梅素对 Aβ寡聚体处理的神经元 SH-SY5Y 细胞和 3×Tg 小鼠的影响。在 3×Tg 小鼠中进行行为测试，以评估杨梅素（14 天，ip）的认知作用。通过 Western blot 评估β-淀粉样前体蛋白（APP）、突触和线粒体蛋白、糖原合成酶激酶 3β（GSK3β）和细胞外调节激酶 2（ERK2）的水平。使用流式细胞术分析、免疫荧光染色和透射电子显微镜评估线粒体功能障碍和反应性氧化应激。
与对照处理相比，我们发现杨梅素处理改善了 3×Tg 小鼠的空间认知和学习记忆。杨梅素改善了 Aβ寡聚体处理的神经元 SH-SY5Y 细胞和 3×Tg 小鼠中的 tau 磷酸化以及突触前和突触后蛋白的减少。此外，杨梅素通过相关的 GSK3β 和 ERK2 信号通路减少活性氧的产生、脂质过氧化和 DNA 氧化，并挽救线粒体功能障碍。
本研究为杨梅素在体外细胞培养和体内阿尔茨海默病小鼠模型中的神经保护机制提供了新的见解。
