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星形胶质细胞通过上调脑源性神经营养因子介导了知母皂苷元-AA13的益智和神经营养作用。

Astrocytes mediated the nootropic and neurotrophic effects of Sarsasapogenin-AA13 via upregulating brain-derived neurotrophic factor.

作者信息

Dong Dong, Mao Yu, Huang Cui, Jiao Qian, Pan Hui, Ma Lei, Wang Rui

机构信息

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and TechnologyShanghai, PR China.

出版信息

Am J Transl Res. 2017 Sep 15;9(9):4015-4025. eCollection 2017.

Abstract

, a widely used traditional Chinese medicine, has previously been shown to have neuroprotective effect. Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of Sarsasapogenin, which is extracted from . The aim of this study is to investigate the nootropic and neurotrophic effects of AA13 and underlying mechanisms. , cell viability of rat primary astrocytes treated with AA13 and neurons cultured with conditioned medium of AA13-treated rat primary astrocytes was tested by MTT assays. , a pharmacological model of cognitive impairment induced by scopolamine was employed and spatial memory of the mice was assessed by Morris water maze. This study found that AA13 increased cell viability of primary astrocytes and AA13-treated astrocyte-conditioned medium enhanced the survival rate of primary neurons. Interestingly, AA13 markedly enhanced the level of BDNF in astrocytes. Furthermore, AA13 (6 mg/kg) improved the cognitive deficits in animal models (p<0.05) and BDNF and PSD95 levels were increased in brain. Therefore, we hypothesize that AA13 exerts nootropic and neurotrophic activities through astrocytes mediated upregulation of BDNF secretion. The results suggest that AA13 could be a potential compound for cognitive impairment after further research.

摘要

[一种广泛使用的中药,先前已被证明具有神经保护作用。知母皂苷元 - AA13(AA13)是从[某种植物]中提取的知母皂苷元的新型合成衍生物。本研究的目的是研究AA13的益智和神经营养作用及其潜在机制。首先,通过MTT法检测用AA13处理的大鼠原代星形胶质细胞的细胞活力以及用AA13处理的大鼠原代星形胶质细胞的条件培养基培养的神经元的细胞活力。其次,采用东莨菪碱诱导的认知障碍药理学模型,通过莫里斯水迷宫评估小鼠的空间记忆。本研究发现,AA13提高了原代星形胶质细胞的细胞活力,且经AA13处理的星形胶质细胞条件培养基提高了原代神经元的存活率。有趣的是,AA13显著提高了星形胶质细胞中脑源性神经营养因子(BDNF)的水平。此外,AA13(6mg/kg)改善了动物模型中的认知缺陷(p<0.05),并且脑中BDNF和突触后密度蛋白95(PSD95)水平升高。因此,我们推测AA13通过星形胶质细胞介导的BDNF分泌上调发挥益智和神经营养活性。结果表明,经过进一步研究,AA13可能是一种治疗认知障碍的潜在化合物。]

需注意,原文中部分植物名称未给出具体内容,翻译时用[某种植物]等进行了标注。

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