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人参皂苷通过恢复阿尔茨海默病大鼠模型中神经递质系统的功能障碍,减轻d-半乳糖和氯化铝诱导的空间记忆损伤。

Ginsenosides attenuate d-galactose- and AlCl-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease.

作者信息

Zhang Yan, Pi Zifeng, Song Fengrui, Liu Zhiqiang

机构信息

National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; School of Chemical and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Jilin 132022, PR China.

National Center for Mass Spectrometry in Changchun, Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China.

出版信息

J Ethnopharmacol. 2016 Dec 24;194:188-195. doi: 10.1016/j.jep.2016.09.007. Epub 2016 Sep 6.

DOI:10.1016/j.jep.2016.09.007
PMID:27612432
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Panax ginseng C.A.Mey. is a traditional Chinese herbal medicine, which has been used to treat Alzheimer's disease (AD) for thousands of years. Ginsenoside is one of the major compounds found in P. ginseng. This study aimed to explore the attenuation of spatial memory impairment by ginsenosides and its correlation with restoring the dysfunction of the neurotransmitter systems in AD model rats to understand the mechanism underlying the anti-AD effect of P. ginseng.

MATERIALS AND METHODS

In this study, the AD model was established by combining d-galactose (d-gal) with AlCl (Al) for 60 days. From day 30, the ginsenosides group was intragastrically administered with ginsenosides for 30 days. The ethology of rats was tested through the Morris water maze test(MWM). Histopathological changes in the hippocampus of rats were observed through hematoxylin and eosin staining. The expressions of amyloid β peptide (Aβ) and phospho-tau (p-tau) in the hippocampus and cortex of rats were detected by immunohistochemistry. A liquid chromatography-mass spectrometry assay was used to measure neurotransmitter concentrations in the hippocampus, cortex, and blood.

RESULTS

Ginsenosides could significantly decrease the escape latency time and the average latency time in the place navigation test and increase the times of crossing the platform area, the percentage of residence time, and the distance in the original platform quadrant in the spatial probe test. Ginsenosides could repair the damage of the hippocampus and reduce the expressions of Aβ and p-tau. Ginsenosides could also increase γ-aminobutyric acid, acetylcholine, and dopamine levels and decrease glutamate and aspartic acid levels in the hippocampus and cortex and increase glycine and serotonin levels in the blood.

CONCLUSIONS

After effectively administrated, ginsenosides attenuate d-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.

摘要

民族药理学相关性

人参是一种传统的中草药,数千年来一直用于治疗阿尔茨海默病(AD)。人参皂苷是人参中发现的主要化合物之一。本研究旨在探讨人参皂苷对空间记忆障碍的改善作用及其与恢复AD模型大鼠神经递质系统功能障碍的相关性,以了解人参抗AD作用的潜在机制。

材料与方法

在本研究中,通过将D-半乳糖(D-gal)与氯化铝(Al)联合使用60天建立AD模型。从第30天起,人参皂苷组大鼠灌胃给予人参皂苷30天。通过莫里斯水迷宫试验(MWM)测试大鼠的行为学。通过苏木精-伊红染色观察大鼠海马的组织病理学变化。采用免疫组织化学法检测大鼠海马和皮质中淀粉样β肽(Aβ)和磷酸化tau蛋白(p-tau)的表达。采用液相色谱-质谱分析法测定海马、皮质和血液中的神经递质浓度。

结果

人参皂苷可显著缩短定位航行试验中的逃避潜伏期和平均潜伏期,并增加空间探索试验中穿越平台区域的次数、停留时间百分比和原平台象限内的距离。人参皂苷可修复海马损伤,降低Aβ和p-tau的表达。人参皂苷还可提高海马和皮质中γ-氨基丁酸、乙酰胆碱和多巴胺水平,降低谷氨酸和天冬氨酸水平,并提高血液中甘氨酸和5-羟色胺水平。

结论

有效给药后人参皂苷可减轻D-半乳糖和铝诱导的空间记忆障碍。其有益作用的可能机制是恢复各种神经递质的功能障碍。

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