Luo Hong-Bin, Shang Nan, Xie Wen-Zhi, Wen De-Jian, Qu Min, Huang Sheng, Fan Sha-Sha, Chen Wei, Mou Nan-Qiao, Liu Xiang-Yu, Chen Qin, Xie Feng-Feng, Li Jun-Xu
Hubei Key Laboratory of Biological Resource Protection and Utilization; Medical College, Hubei University for Nationalities; Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities, Enshi, Hubei Province, China.
Medical College, Hubei University for Nationalities; Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities, Enshi, Hubei Province, China.
Neural Regen Res. 2018 May;13(5):915-922. doi: 10.4103/1673-5374.232487.
Large-scale epidemiological studies have found that hyperhomocysteinemia is a powerful, independent risk factor for Alzheimer's disease. Trillium tschonoskii maxim is a traditional Chinese medicine that is used to promote memory. However, scientific understanding of its mechanism of action is limited. This report studied the potential neuroprotective effects of Trillium tschonoskii maxim extract against homocysteine-induced cognitive deficits. Rats were intravenously injected with homocysteine (400 μg/kg) for 14 days to induce a model of Alzheimer's disease. These rats were then intragastrically treated with Trillium tschonoskii maxim extract (0.125 or 0.25 g/kg) for 7 consecutive days. Open field test and Morris water maze test were conducted to measure spontaneous activity and learning and memory abilities. Western blot assay was used to detect the levels of Tau protein and other factors involved in Tau phosphorylation in the hippocampus. Immunohistochemical staining was used to examine Tau protein in the hippocampus. Golgi staining was applied to measure hippocampal dendritic spines. Our results demonstrated that homocysteine produced learning and memory deficits and increased levels of Tau phosphorylation, and diminished the activity of catalytic protein phosphatase 2A. The total number of hippocampal dendritic spines was also decreased. Trillium tschonoskii maxim extract treatment reversed the homocysteine-induced changes. The above results suggest that Trillium tschonoskii maxim extract can lessen homocysteine-induced abnormal Tau phosphorylation and improve cognitive deterioration such as that present in Alzheimer's disease.
大规模流行病学研究发现,高同型半胱氨酸血症是阿尔茨海默病一个强大的独立危险因素。延龄草是一种用于增强记忆力的传统中药。然而,对其作用机制的科学认识有限。本报告研究了延龄草提取物对同型半胱氨酸诱导的认知缺陷的潜在神经保护作用。给大鼠静脉注射同型半胱氨酸(400μg/kg),持续14天,以诱导阿尔茨海默病模型。然后连续7天给这些大鼠灌胃给予延龄草提取物(0.125或0.25g/kg)。进行旷场试验和莫里斯水迷宫试验以测量自发活动以及学习和记忆能力。采用蛋白质免疫印迹法检测海马体中Tau蛋白水平以及其他参与Tau蛋白磷酸化的因子。采用免疫组织化学染色法检测海马体中的Tau蛋白。采用高尔基染色法测量海马体树突棘。我们的结果表明,同型半胱氨酸导致学习和记忆缺陷,增加Tau蛋白磷酸化水平,并降低催化蛋白磷酸酶2A的活性。海马体树突棘的总数也减少。延龄草提取物治疗逆转了同型半胱氨酸诱导的变化。上述结果表明,延龄草提取物可以减轻同型半胱氨酸诱导的异常Tau蛋白磷酸化,并改善认知衰退,如阿尔茨海默病中出现的情况。