Xu Ting-Ting, Zhang Yang, He Jia-Yang, Luo Dan, Luo Yi, Wang Yi-Jie, Liu Wei, Wu Jun, Zhao Wei, Fang Jiansong, Guan Li, Huang Shun, Wang Hong, Lin Li, Zhang Shi-Jie, Wang Qi
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Cell Physiol Biochem. 2018;46(1):107-117. doi: 10.1159/000488414. Epub 2018 Mar 20.
BACKGROUND/AIMS: Alzheimer disease (AD) is a common neurodegenerative disease that is characterized by the deposition of beta-amyloid peptide and formation of intracellular neurofibrillary tangles. Due to the failure of various clinical trials of novel drugs for AD, effective drugs for AD treatment are urgently required.
In this study, we used the classic APP/PS1 mouse model to explore the neuroprotective effects of a new compound, bajijiasu, and the mechanisms involved. Behavioral tests and western blotting were performed to assess the beneficial effects of bajijiasu in APP/PS1 mice.
Morris water maze and Y-maze test results showed that oral administration of bajijiasu (35 mg/kg/day and 70 mg/kg/day) improved learning and memory abilities in APP/PS1 mice. Bajijiasu reduced ROS and MDA levels in both the hippocampus and cortex. Moreover, western blotting results showed that bajijiasu protected neurons from apoptosis, elevated the expression levels of neurotrophic factors, and alleviated endoplasmic reticulum stress in both the hippocampus and cortex.
These results indicate that the mechanisms underlying the effects of bajijiasu on AD might be related to beta-amyloid-downstream pathologies, particularly endoplasmic reticulum stress.
背景/目的：阿尔茨海默病（AD）是一种常见的神经退行性疾病，其特征是β-淀粉样肽沉积和细胞内神经原纤维缠结的形成。由于针对AD的新型药物的各种临床试验均告失败，因此迫切需要有效的AD治疗药物。
在本研究中，我们使用经典的APP/PS1小鼠模型来探索一种新化合物八角加素的神经保护作用及其相关机制。进行行为测试和蛋白质免疫印迹分析以评估八角加素对APP/PS1小鼠的有益作用。
莫里斯水迷宫和Y迷宫测试结果表明，口服八角加素（35毫克/千克/天和70毫克/千克/天）可改善APP/PS1小鼠的学习和记忆能力。八角加素降低了海马体和皮质中的活性氧（ROS）和丙二醛（MDA）水平。此外，蛋白质免疫印迹分析结果表明，八角加素可保护神经元免受凋亡，提高神经营养因子的表达水平，并减轻海马体和皮质中的内质网应激。
这些结果表明，八角加素对AD的作用机制可能与β-淀粉样蛋白下游病理变化有关，尤其是内质网应激。
