基于网络药理学的脉络舒通丸治疗痔疮作用机制研究

Mechanism of Mailuo Shutong Pills in the Treatment of Hemorrhoids Based on Network Pharmacology

目的:探讨脉络舒通丸治疗痔疮的潜在活性成分及可能的作用机制。方法:通过中药系统药理学数据库与分析平台、DisGeNET和GeneCards等数据库获取脉络舒通丸中的化学成分和痔疮的相关靶点。将交集靶点导入STRING数据库进行分析,分析结果导入Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络图、脉络舒通丸化学成分-靶点网络图、药物-成分-靶点-通路网络图。通过R语言对关键靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。使用AutoDockTools软件对脉络舒通丸中的活性成分与其对应的关键靶点进行分子对接验证。结果:筛选得到脉络舒通丸中的215个化合物、310个相关靶点、148个化合物与疾病交集靶点,得到关键靶点蛋白激酶B(Akt)1、肿瘤蛋白p53(TP53)、白细胞介素6(IL-6)、表皮生长因子受体(EGFR)、血管内皮生长因子A(VEGFA)、雌激素受体1(ESR1)、缺氧诱导因子1A(HIF1A)和肿瘤坏死因子(TNF)。对PPI网络的分析共得到161条KEGG通路,3 041条GO功能条目。在GO功能条目中,包括2 706条生物过程、140条细胞成分和195条分子功能的相关条目。分子对接结果表明,槲皮素、芒柄花素、木犀草素、汉黄芩素等化合物与Akt1、TNF、TP53、IL-6、EGFR、VEGFA、ESR1有较好的结合活性。结论:脉络舒通丸治疗痔疮是基于多成分、多靶点的作用机制,本研究为下一步的相关机制验证提供了理论基础。

OBJECTIVE: To probe into the potential active components and possible mechanism of Mailuo Shutong pills in the treatment of hemorrhoids. METHODS: Chemical constituents of Mailuo Shutong pills and the related targets of hemorrhoids were obtained by Traditional Chinese medicine systems pharmacology database and analysis platform, DisGeNET, GeneCards and other databases. The intersection targets were imported into STRING database for analysis, and the analysis results were imported into Cytoscape software to construct protein-protein interaction(PPI) network diagram, Mailuo Shutong pills chemical components-target network diagram and drug-component-target-pathway network. The key targets were analyzed by gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome(KEGG) pathway enrichment analysis by R language. AutoDockTools software was used to verify the molecular docking between the active components of Mailuo Shutong pills and the corresponding key targets. RESULTS: A total of 215 compounds, 310 related targets, and 148 compound and disease intersection targets were screened. Key targets including protein kinase B(Akt) 1, tumor protein p53(TP53), interleukin(IL) 6, epidermal growth factor receptor(EGFR), vascular endothelial growth factor A(VEGFA), ESR1, HIF1 A and tumor necrosis factor(TNF) were identified. Based on the analysis of PPI network, there were 161 KEGG pathways and 3 041 GO functional entries were obtained. In the GO functional items, there were 2 706 biological process related items, 140 cellular components, and 195 molecular function related items. The results of molecular docking showed that quercetin, formononetin, luteolin, wogonin, kaempferol and other compounds had good binding activity with Akt1, TNF, TP53, IL-6, EGFR, VEGFA and ESR1. CONCLUSIONS: Mailuo Shutong pills in the treatment of hemorrhoids is based on the mechanism of multi-components and multi-targets. This study provides theoretical basis for further verification of related mechanisms.