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五味子乙素对使用β-淀粉样蛋白Aβ介导的SH-SY5Y神经细胞系损伤的阿尔茨海默病模型的影响及潜在机制。

The influence of Schisandrin B on a model of Alzheimer's disease using β-amyloid protein Aβ-mediated damage in SH-SY5Y neuronal cell line and underlying mechanisms.

作者信息

Zhang Ming, Zheng Hong-Xia, Gao Yang-Yang, Zheng Bo, Liu Jing-Ping, Wang He, Yang Zhan-Jun, Zhao Zhi-Ying

机构信息

a Department of Human Anatomy , Baotou Medical College , Inner Mongolia , China.

b Faculty of Foreign languages s , Baotou Teacher's college , Inner Mongolia , China.

出版信息

J Toxicol Environ Health A. 2017;80(22):1199-1205. doi: 10.1080/15287394.2017.1367133. Epub 2017 Sep 11.

Abstract

Schisandrin B, an active substance, is derived from Chinese herb fruit Wuweizi, which exerts various pharmacological activities and has displayed significant beneficial effects in ameliorating Alzheimer's disease (AD). The aim of this study was to further extend our examination for the use of schisandrin B extract in the potential treatment of AD effects by investigating DNA methylation (DNMT), known to be modified in this disease using SH-SY5Y neuronal cell line exposed to β-amyloid protein (Aβ). In particular, the purpose of this investigation was to examine alterations in mRNA and protein expression of DNMT. Data demonstrated that schisandrin B blocked Aβ-mediated injury in SH-SY5Y neuronal cell line as evidenced by a restoration of cellular morphology and cell viability to approximate control levels at the highest 10 μg/ml Schisandrin B. Incubation with Aβ significantly decreased mRNA and protein expression of DNMT3A and DNMT1 in SH-SY5Y neuronal cell line. Incubation with Aβ followed by 24 treatment with schisandrin B significantly inhibited the Aβ -induced changes in mRNA and protein expression of DNMT3A and DNMT3B in a concentration-dependent manner. It is of interest that the mRNA expression of DNMT3A and DNMT1 were significantly higher than control. Data thus indicate schisandrin B was effective in inhibiting the actions of Aβ on cell survival and morphology and that DNA methylation may be associated with the beneficial findings.

摘要

五味子乙素是一种活性物质,源自中药五味子果实,具有多种药理活性,在改善阿尔茨海默病(AD)方面已显示出显著的有益效果。本研究的目的是通过研究DNA甲基化转移酶(DNMT),进一步扩展我们对五味子乙素提取物在AD潜在治疗作用的研究,已知在该疾病中DNMT会发生改变,使用暴露于β-淀粉样蛋白(Aβ)的SH-SY5Y神经细胞系进行研究。具体而言,本研究的目的是检测DNMT的mRNA和蛋白表达的变化。数据表明,五味子乙素可阻断Aβ介导的SH-SY5Y神经细胞系损伤,在最高浓度10μg/ml五味子乙素时,细胞形态和细胞活力恢复到接近对照水平即可证明。与Aβ孵育显著降低了SH-SY5Y神经细胞系中DNMT3A和DNMT1的mRNA和蛋白表达。先用Aβ孵育,再用五味子乙素处理24小时,可显著抑制Aβ诱导的DNMT3A和DNMT3B的mRNA和蛋白表达变化,且呈浓度依赖性。有趣的是,DNMT3A和DNMT1的mRNA表达显著高于对照。因此,数据表明五味子乙素可有效抑制Aβ对细胞存活和形态的作用,且DNA甲基化可能与这些有益结果相关。

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