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基于网络药理学方法揭示大血藤治疗溃疡性结肠炎的作用机制。

Revealing mechanism of Caulis Sargentodoxae for the treatment of ulcerative colitis based on network pharmacology approach.

机构信息

Graduate School, Southwest Medical University, Luzhou, Sichuan 646000, China.

Department of General Surgery, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital, Chengdu, Sichuan 610051, China.

出版信息

Biosci Rep. 2021 Jan 29;41(1). doi: 10.1042/BSR20204005.

Abstract

OBJECTIVE

The traditional Chinese medicine Caulis Sargentodoxae is widely used in the treatment of ulcerative colitis (UC), but the mechanism remains unknown. The present study aims to reveal its effective components, targets and pathways through network pharmacology and bioinformatics approaches.

MATERIALS AND METHODS

Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to identify effective components. The ligand-based targets prediction was achieved through SwissTargetPrediction and TargetNet. UC-related targets were identified using Gene Expression Omnibus (GEO) data and DisGeNET. The common targets of disease and components were constructed and analyzed by PPI network. Lastly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses are used to explain the functions of these common targets. Components-Targets-Pathways network was visualized and analyzed to further reveal the connection between the components and targets.

RESULTS

Eight active components and 102 key targets were identified to play an important role in UC. These targets were related to regulation of protein serine/threonine kinase activity, positive regulation of cell motility, response to molecule of bacterial origin, response to toxic substance, ERK1 and ERK2 cascade, peptidyl-tyrosine modification, inositol lipid-mediated signaling, cellular response to drug, regulation of inflammatory response and leukocyte migration. Moreover, HIF-1 signaling pathway and PI3K-Akt signaling pathway were the key targets involved in UC-related signaling pathways.

CONCLUSION

The eight active components of Caulis Sargentodoxae mainly play a therapeutic role for UC through synergistic regulation of HIF-1 signaling pathway and PI3K-Akt signaling pathway.

摘要

目的

中药大血藤在溃疡性结肠炎(UC)的治疗中被广泛应用,但作用机制尚不清楚。本研究旨在通过网络药理学和生物信息学方法揭示其有效成分、靶点和通路。

材料与方法

采用中药系统药理学数据库和分析平台(TCMSP)筛选有效成分,通过 SwissTargetPrediction 和 TargetNet 进行配体靶点预测,利用基因表达综合数据库(GEO)和疾病基因数据库(DisGeNET)挖掘 UC 相关靶点,构建并分析疾病和成分的共同靶点 PPI 网络,最后进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,阐述这些共同靶点的功能。通过构建成分-靶点-通路网络图,进一步揭示成分与靶点之间的联系。

结果

筛选出 8 个活性成分和 102 个关键靶点,这些靶点与蛋白丝氨酸/苏氨酸激酶活性的调节、细胞运动的正调控、对细菌来源分子的反应、对有毒物质的反应、ERK1 和 ERK2 级联、肽基酪氨酸修饰、肌醇脂质介导的信号转导、细胞对药物的反应、炎症反应和白细胞迁移的调节等有关。此外,HIF-1 信号通路和 PI3K-Akt 信号通路是与 UC 相关信号通路有关的关键靶点。

结论

大血藤的 8 种活性成分主要通过协同调节 HIF-1 信号通路和 PI3K-Akt 信号通路,发挥对 UC 的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66f1/7846960/5f6edf7b28d1/bsr-41-bsr20204005-g1.jpg

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