Alzheimer's disease (AD) is a multi-factorial neurodegenerative disorder with abnormal accumulation of amyloid-β (Aβ) plaques, neuroinflammation and impaired neurogenesis. Mounting evidences suggest that single-target drugs have limited effects on clinical treatment and alternative or multiple targets are required. In recent decades, natural compounds and their derivatives have gained increasing attention in AD drug discovery due to their inherently enormous chemical and structural diversity. In this study, we demonstrated that naringin dihydrochalcone (NDC), a widely used dietary sweetener with strong antioxidant activity, improved the cognitive function of transgenic AD mice. Pathologically, NDC attenuated Aβ deposition in AD mouse brain. Furthermore, NDC reduced periplaque activated microglia and astrocytes, indicating the inhibition of neuroinflammation. It also enhanced neurogenesis as investigated by BrdU/NeuN double labeling. Additionally, the inhibition of Aβ level and neuroinflammation by NDC treatment was also observed in an AD cell model or a microglia cell line. Taken together, our study indicated that NDC might be a potential therapeutic agent for the treatment of AD against multiple targets that include Aβ pathology, neuroinflammation and neurogenesis.

中文翻译：

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柚皮苷二氢查耳酮可改善APP / PS1转基因小鼠的认知缺陷和神经病理学。

阿尔茨海默氏病（AD）是一种多因素神经退行性疾病，伴有淀粉样β（Aβ）斑块异常积聚，神经炎症和神经发生受损。越来越多的证据表明，单一目标药物对临床治疗的作用有限，因此需要替代目标或多个目标。近几十年来，天然化合物及其衍生物因其固有的巨大化学和结构多样性而在AD药物开发中受到越来越多的关注。在这项研究中，我们证明了柚皮苷二氢查尔酮（NDC）是一种广泛使用的具有强抗氧化活性的饮食甜味剂，可改善转基因AD小鼠的认知功能。病理上，NDC减弱了AD小鼠大脑中的Aβ沉积。此外，NDC减少了斑块活化的小胶质细胞和星形胶质细胞，说明抑制了神经炎症。如BrdU / NeuN双重标记所研究，它还增强了神经发生。另外，在AD细胞模型或小胶质细胞系中也观察到通过NDC处理对Aβ水平的抑制和神经炎症。两者合计，我们的研究表明NDC可能是针对多种靶标（包括Aβ病理学，神经炎症和神经发生）治疗AD的潜在治疗剂。