Ginsenosides attenuate D-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease
Ginsenosides attenuate D-galactose- and AlCl3-inducedspatial memory impairment by restoring the dysfunction of the neurotransmitter systems in the rat model of Alzheimer's disease
复制标题
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来减轻 d-半乳糖和 AlCl3 诱导的空间记忆障碍
DOI：
10.1016/j.jep.2016.09.007
复制
发表时间：
2016
影响因子：
5.4
通讯作者：
Liu Zhiqiang
中科院分区：
文献类型：
--
作者：
Zhang Yan;Pi Zifeng;Song Fengrui;Liu Zhiqiang
人参是一种传统的中草药，数千年来一直被用于治疗阿尔茨海默病（AD）。ginsengC.A.Mey.is人参皂苷是人参中的主要成分之一。参本研究旨在探讨三七总皂甙对AD模型大鼠空间记忆障碍的改善作用及其与恢复神经递质系统功能障碍的关系，以了解三七总皂甙抗AD的作用机制。本研究采用d-半乳糖（d-gal）与三氯化铝（Al）联合作用60天的方法建立AD模型。从第30天开始，黄芪皂苷组灌胃给予黄芪皂苷30天。采用Morris水迷宫实验（MWM）检测大鼠行为学。苏木精-伊红染色观察大鼠海马组织学变化。采用免疫组织化学方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-质谱联用法测定海马、皮层和血液中神经递质的浓度。结果人参皂甙能显著缩短定位导航实验中的逃避潜伏期和平均潜伏期，增加空间探测实验中穿越平台区的次数、停留时间百分比和原平台象限的距离。人参皂甙可修复海马损伤，降低Aβ和p-tau蛋白的表达。人参皂甙还可以增加γ-氨基丁酸，乙酰胆碱，多巴胺的水平，降低谷氨酸和天冬氨酸在海马和皮层的水平，提高甘氨酸和5-羟色胺在blood.ConclusionsAfter有效给药，人参皂甙减轻半乳糖和铝诱导的空间记忆障碍。其可能的作用机制是恢复多种神经递质的功能障碍。
Ethnopharmacological relevancePanax ginsengC.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 inP. 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 ofP. ginseng.Materials and methodsIn this study, the AD model was established by combiningd-galactose (d-gal) with AlCl3(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.ResultsGinsenosides 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.ConclusionsAfter effectively administrated, ginsenosides attenuated-gal- and Al-induced spatial memory impairment. The possible mechanism of the beneficial effect is restoring the dysfunction of various neurotransmitters.