BACKGROUND Alzheimer's disease (AD) is one of the most prevalent diseases with rapidly increasing numbers, but there is still no medication to treat or stop the disease. Previous data on coumarins suggests that scopoletin may have potential benefits in AD. OBJECTIVE Evaluate the therapeutic potential of the coumarins with natural origin - scopoletin and pteryxin- in a 5xFAD mouse model of AD. METHODS Both compounds were administered at two doses to 12-month-old mice, which represent severe AD pathology. The effects of coumarins were assessed on cognition in mouse experiments. Changes in the overall brain proteome were evaluated using LCMS/ MS analyses. RESULTS The Morris water maze test implicated that a higher dose of pteryxin (16 mg/kg) significantly improved learning, and the proteome analysis showed pronounced changes of specific proteins upon pteryxin administration. The amyloid-β precursor protein, glial fibrillary acid protein, and apolipoprotein E protein which are highly associated with AD, were among the differentially expressed proteins at the higher dose of the pteryxin. CONCLUSION Overall, pteryxin may be evaluated further as a disease-modifying agent in AD pathology in the late stages of AD.

中文翻译：

---

在 5xFAD 阿尔茨海默病小鼠模型中，蝶呤和莨菪碱的分子效应。

背景技术阿尔茨海默病(Alzheimer's disease，AD)是最流行的疾病之一，其数量迅速增加，但仍然没有治疗或阻止该疾病的药物。先前有关香豆素的数据表明，东莨菪碱可能对 AD 有潜在益处。目的 评估天然来源的香豆素 - 东莨菪碱和翼霉素 - 在 5xFAD 小鼠 AD 模型中的治疗潜力。方法 两种化合物均以两个剂量给予 12 个月大的小鼠，这些小鼠代表严重的 AD 病理学。在小鼠实验中评估了香豆素对认知的影响。使用 LCMS/MS 分析评估整体脑蛋白质组的变化。结果 莫里斯水迷宫测试表明，较高剂量的翼霉素（16 mg/kg）显着改善了学习，蛋白质组分析显示，在 pteryxin 给药后，特定蛋白质发生了显着变化。与 AD 高度相关的淀粉样蛋白-β 前体蛋白、神经胶质纤维酸性蛋白和载脂蛋白 E 蛋白在较高剂量的翼状蛋白中属于差异表达的蛋白质。结论 总体而言，翼状胬肉可作为 AD 晚期 AD 病理学中的疾病调节剂进行进一步评估。