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采用高效液相色谱-傅里叶变换离子回旋共振质谱联用技术研究红景天提取物对阿尔茨海默病的脑代谢组学保护作用。

Brain metabolomics study for the protective effects of Rhodiola crenulata extract on Alzheimer's disease by HPLC coupled with Fourier transform-ion cyclotron resonance mass spectrometry.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.

Dalian Customs District, Dalian, P. R. China.

出版信息

J Sep Sci. 2020 Aug;43(16):3216-3223. doi: 10.1002/jssc.201901314. Epub 2020 Jun 22.

Abstract

In order to investigate the protective effects of Rhodiola crenulata extract on Alzheimer's disease, a brain metabolomics study in rats was conducted by high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry. Rat model was constructed by bilateral hippocampal injection of amyloid-β peptide and immunohistochemistry was performed to evaluate the pharmacological effect of Rhodiola crenulata extract. Multivariate statistical analysis was used to discover potential biomarkers in rat brain and related metabolic pathways analysis was conducted to elucidate the action mechanism of Rhodiola crenulata extract. As a result, a total of 19 metabolites contributing to Alzheimer's disease progress were identified and nine of them were restored to the normal levels after drug administration. Pathway analysis revealed that the protective effects of Rhodiola crenulata extract are related to the regulation of glutathione metabolism and arachidonic acid metabolism in rat brain. In conclusion, this work demonstrates that the developed metabolomics method is useful to investigate the protective effects of Rhodiola crenulata extract against Alzheimer's disease. These outcomes may further provide reliable evidence to illuminate the intervention mechanism of other traditional Chinese medicines on Alzheimer's disease.

摘要

为了研究红景天提取物对阿尔茨海默病的保护作用,采用高效液相色谱-傅里叶变换离子回旋共振质谱联用技术对大鼠进行了脑代谢组学研究。通过双侧海马内注射淀粉样蛋白-β肽构建大鼠模型,并通过免疫组织化学方法评价红景天提取物的药理作用。采用多元统计分析方法发现大鼠脑组织中的潜在生物标志物,并进行相关代谢途径分析,阐明红景天提取物的作用机制。结果共鉴定出 19 种与阿尔茨海默病进展相关的代谢物,其中 9 种在给药后恢复到正常水平。通路分析表明,红景天提取物的保护作用与大鼠脑组织中谷胱甘肽代谢和花生四烯酸代谢的调节有关。综上所述,本研究表明所建立的代谢组学方法可用于研究红景天提取物防治阿尔茨海默病的作用机制。这些结果可能为阐明其他中药对阿尔茨海默病的干预机制提供可靠依据。

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