Table_1_Bazhu Decoction, a Traditional Chinese Medical Formula, Ameliorates Cognitive Deficits in the 5xFAD Mouse Model of Alzheimer’s Disease.docx

Alzheimer’s disease (AD) is the most common neurodegenerative disorder associated with aging. There are currently no effective treatments for AD. Bazhu decoction (BZD), a traditional Chinese medicine (TCM) formula, has been employed clinically to alleviate AD. However, the underlying molecular mechanisms are still unclear. Here we found that middle- and high-doses of BZD ameliorated the behavioral aspects of 5xFAD transgenic mice in elevated plus maze, Y maze and Morris water maze tests. Moreover, BZD reduced the protein levels of BACE1 and PS1, resulting in a reduction of Aβ plaques. We also identified a beneficial effect of BZD on oxidative stress by attenuating MDA levels and SOD activity in the brains of 5xFAD mice. Together, these results indicate that BZD produces a dose-dependent positive effect on 5xFAD transgenic mouse model by decreasing APP processing and Aβ plaques, and by ameliorating oxidative damage. BZD may play a protective role in the cognitive and anxiety impairments and may be a complementary therapeutic option for AD.

阿尔茨海默病（AD）是最常见的与衰老相关的神经退行性疾病，目前尚无有效的临床治疗手段。八味汤（BZD）作为一种传统中药（TCM）方剂，已在临床中用于缓解阿尔茨海默病的症状，但其潜在的分子机制仍不明确。本研究发现，中、高剂量的八味汤可改善5xFAD转基因小鼠在高架十字迷宫、Y型迷宫及莫里斯水迷宫实验中的行为学表型。此外，八味汤可降低β位淀粉样前体蛋白裂解酶1（BACE1）与早老素1（PS1）的蛋白水平，进而减少Aβ斑块的形成。我们还证实，八味汤可通过降低5xFAD小鼠脑内丙二醛（MDA）水平、提升超氧化物歧化酶（SOD）活性，发挥对抗氧化应激的有益作用。综上，上述结果表明，八味汤可通过抑制淀粉样前体蛋白（APP）加工、减少Aβ斑块沉积，并改善氧化损伤，对5xFAD转基因小鼠模型产生剂量依赖性的积极干预效果。八味汤或可改善阿尔茨海默病相关的认知与焦虑障碍，有望成为阿尔茨海默病的辅助治疗选择。