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毛蕊花糖苷(麦角硫因)对D-半乳糖和氯化铝联合诱导的衰老小鼠模型记忆增强作用的机制

The Mechanism of Memory Enhancement of Acteoside (Verbascoside) in the Senescent Mouse Model Induced by a Combination of D-gal and AlCl3.

作者信息

Peng Xiao-Ming, Gao Li, Huo Shi-Xia, Liu Xin-Min, Yan Ming

机构信息

Prescription Laboratory of Xinjiang Traditional Uyghur Medicine, Xinjiang Institute of Traditional Uyghur Medicine, Urumqi, Xinjiang, 830049, China.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100193, China.

出版信息

Phytother Res. 2015 Aug;29(8):1137-44. doi: 10.1002/ptr.5358. Epub 2015 Apr 21.

DOI:10.1002/ptr.5358
PMID:25900087
Abstract

Acteoside (verbsacoside), one of the main active phenylethanoid glycosides from Cistanche deserticola, is known to have antioxidant and neuroprotective activity, and herbs containing it are used to enhance memory. However, there is relatively little direct experimental evidence to support the use of acteoside in Alzheimer's disease (AD). The purpose of this study was to elucidate the effects of acteoside in improving learning and memory, using a mouse model of senescence induced by a combination of d-galactose and AlCl3 , and investigate its potential mechanisms compared with the positive controls vitamin E and piracetam. Acteoside was administered intragastrically at doses of 30, 60 and 120 mg/kg/day for 30 days after AD was induced. Memory function was evaluated using a step-down test. The number of neuron was analysed by haematoxylin and eosin staining and the number of Nissl bodies by Nissl staining. The expression of caspase-3 protein in hippocampus was detected by immunohistochemistry and western blot. Nitric oxide and total nitric oxide synthase level in hippocampus were also assessed. Our results showed that the latency of step down was shortened in AD model mice and the number of errors decreased after treatment with all doses of acteoside. Neurons and Nissl bodies in the hippocampus were increased significantly with higher doses (60 and 120 mg/kg/day) of acteoside. The content of nitric oxide, the activity of nitric oxide synthase and the expression of caspase-3 protein were decreased by 120 mg/kg/day acteoside compared with that of the AD model group. Our results support the results obtained previously using the Morris maze test in the same mouse model of senescence, and the use of traditional medicinal herbs containing acteoside for neuroprotection and memory loss.

摘要

松果菊苷(毛蕊花糖苷)是肉苁蓉中主要的活性苯乙醇苷之一,已知具有抗氧化和神经保护活性,含有该成分的草药被用于增强记忆力。然而,相对较少有直接的实验证据支持将松果菊苷用于治疗阿尔茨海默病(AD)。本研究的目的是利用D-半乳糖和AlCl3联合诱导衰老的小鼠模型,阐明松果菊苷在改善学习和记忆方面的作用,并与阳性对照维生素E和吡拉西坦相比,研究其潜在机制。在诱导AD后,以30、60和120mg/kg/天的剂量灌胃给予松果菊苷,持续30天。使用跳台试验评估记忆功能。通过苏木精-伊红染色分析神经元数量,通过尼氏染色分析尼氏体数量。通过免疫组织化学和蛋白质印迹法检测海马中caspase-3蛋白的表达。还评估了海马中的一氧化氮和总一氧化氮合酶水平。我们的结果表明,在AD模型小鼠中,所有剂量的松果菊苷治疗后跳台潜伏期缩短,错误次数减少。高剂量(60和120mg/kg/天)的松果菊苷可显著增加海马中的神经元和尼氏体。与AD模型组相比,120mg/kg/天的松果菊苷可降低一氧化氮含量、一氧化氮合酶活性和caspase-3蛋白的表达。我们的结果支持先前在同一衰老小鼠模型中使用莫里斯水迷宫试验获得的结果,以及使用含有松果菊苷的传统草药进行神经保护和治疗记忆丧失的作用。

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