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整合系统生物学和蛋白质组学策略,探索丹参饮干预动脉粥样硬化的药理机制。

Integrating systematic biological and proteomics strategies to explore the pharmacological mechanism of danshen yin modified on atherosclerosis.

机构信息

The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, China.

Hunan University of Chinese Medicine, Changsha, China.

出版信息

J Cell Mol Med. 2020 Dec;24(23):13876-13898. doi: 10.1111/jcmm.15979. Epub 2020 Nov 2.

Abstract

This research utilized the systematic biological and proteomics strategies to explore the regulatory mechanism of Danshen Yin Modified (DSYM) on atherosclerosis (AS) biological network. The traditional Chinese medicine database and HPLC was used to find the active compounds of DSYM, Pharmmapper database was used to predict potential targets, and OMIM database and GeneCards database were used to collect AS targets. String database was utilized to obtain the other protein of proteomics proteins and the protein-protein interaction (PPI) data of DSYM targets, AS genes, proteomics proteins and other proteins. The Cytoscape 3.7.1 software was utilized to construct and analyse the network. The DAVID database is used to discover the biological processes and signalling pathways that these proteins aggregate. Finally, animal experiments and proteomics analysis were used to further verify the prediction results. The results showed that 140 active compounds, 405 DSYM targets and 590 AS genes were obtained, and 51 differentially expressed proteins were identified in the DSYM-treated ApoE-/- mouse AS model. A total of 4 major networks and a number of their derivative networks were constructed and analysed. The prediction results showed that DSYM can regulate AS-related biological processes and signalling pathways. Animal experiments have also shown that DSYM has a therapeutic effect on ApoE-/-mouse AS model (P < .05). Therefore, this study proposed a new method based on systems biology, proteomics, and experimental pharmacology, and analysed the pharmacological mechanism of DSYM. DSYM may achieve therapeutic effects by regulating AS-related signalling pathways and biological processes found in this research.

摘要

本研究采用系统生物学和蛋白质组学策略,探讨丹参饮(DSYM)调控动脉粥样硬化(AS)生物学网络的作用机制。利用中药数据库和高效液相色谱法寻找 DSYM 的活性化合物,Pharmmapper 数据库预测潜在靶点,OMIM 数据库和 GeneCards 数据库收集 AS 靶点。String 数据库获取蛋白质组学蛋白的其他蛋白和 DSYM 靶点、AS 基因、蛋白质组学蛋白和其他蛋白的蛋白-蛋白相互作用(PPI)数据。使用 Cytoscape 3.7.1 软件构建和分析网络。利用 DAVID 数据库发现这些蛋白聚集的生物学过程和信号通路。最后,通过动物实验和蛋白质组学分析进一步验证预测结果。结果表明,获得了 140 种活性化合物、405 个 DSYM 靶点和 590 个 AS 基因,并在 DSYM 处理的 ApoE-/-小鼠 AS 模型中鉴定出 51 个差异表达蛋白。构建和分析了 4 个主要网络及其衍生网络。预测结果表明,DSYM 可以调节 AS 相关的生物学过程和信号通路。动物实验也表明,DSYM 对 ApoE-/-小鼠 AS 模型具有治疗作用(P<.05)。因此,本研究提出了一种基于系统生物学、蛋白质组学和实验药理学的新方法,并分析了 DSYM 的药理学机制。DSYM 可能通过调节本研究中发现的与 AS 相关的信号通路和生物学过程来发挥治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b7e/7753997/8eb0c74f92f5/JCMM-24-13876-g001.jpg

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