School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China.
School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, 110016, People's Republic of China.
Neuromolecular Med. 2020 Sep;22(3):370-383. doi: 10.1007/s12017-020-08595-2. Epub 2020 Mar 5.
Alzheimer's disease (AD), one of the most common neurodegenerative diseases, threatens people's health. Based on the theory of traditional Chinese medicine (TCM) efficacy and treatment theory, we first proposed the Alpinia oxyphylla-Schisandra chinensis herb pair (ASHP) for finding a candidate of AD treatment. This study aimed at exploring the effects of ASHP on improving the cognitive function and neurodegeneration, and revealing the possible mechanism. In this study, an amyloid-β (Aβ) induced AD model was established in mice via intracerebroventricular injection. The Y-maze test and Morris water maze test were carried out to observe the behavioral change of mice, which showed that ASHP significantly ameliorated cognitive impairment. In addition, ASHP reduced amyloid-β deposition and downregulated the hyperphosphorylation of tau via immunofluorescence assay and western blot analysis, respectively. Subsequently we focused on the PI3K/Akt pathway that is a classical pathway related to nervous system diseases. It also noticeably ASHP improved the histopathological changes in the hippocampus and cortex. Moreover, it was found that ASHP could upregulate the PI3K/Akt/Gsk-3β/CREB signaling pathway in N2a-SwedAPP cells. Taken together, it suggests that ASHP might reverse cognitive deficits and neurodegeneration via PI3K/Akt/Gsk-3β/CREB pathway.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，威胁着人们的健康。基于中医功效和治疗理论，我们首先提出益智-五味子药对（ASHP），以期找到治疗 AD 的候选药物。本研究旨在探讨 ASHP 改善认知功能和神经退行性变的作用，并揭示其可能的机制。本研究通过侧脑室注射建立了淀粉样β（Aβ）诱导的 AD 模型。通过 Y 迷宫试验和 Morris 水迷宫试验观察小鼠的行为变化，结果表明 ASHP 可显著改善认知障碍。此外，免疫荧光和 Western blot 分析分别显示，ASHP 可减少 Aβ 沉积和下调 tau 的过度磷酸化。随后，我们集中研究了与神经系统疾病相关的经典通路 PI3K/Akt 通路。结果还表明，ASHP 可改善海马和皮质的组织病理学变化。此外，在 N2a-SwedAPP 细胞中发现 ASHP 可上调 PI3K/Akt/Gsk-3β/CREB 信号通路。综上所述，ASHP 可能通过 PI3K/Akt/Gsk-3β/CREB 通路逆转认知功能障碍和神经退行性变。
