基于网络药理学和分子对接探讨梓木草抗炎作用机制

Anti-inflammatory mechanisms of Lithospermum Zollinger DC by network pharmacology and molecular docking

目的基于网络药理学和分子对接探讨梓木草抗炎的作用机制。方法2023年1—3月,首先利用网络药理学研究方法在文献中检索梓木草成分,并通过TCMSP数据库、PubChem数据库获取成分结构式及3D结构,同时将成分结构导入Swiss Target Prediction数据库中获取相应靶点。其次,在DisGeNET数据库、GeneCards数据库获取炎症的相关靶点,并利用微生信平台获取梓木草成分与炎症的共同基因靶点,采用Cytoscape3.9.0软件构建“梓木草-成分-潜在作用靶点-炎症”网络。再次,利用STRING数据库获取梓木草抗炎蛋白质-蛋白质相互作用(PPI)网络,DAVID平台进行基因本体(GO)分析及京都基因和基因组数据库(KEGG)信号通路富集分析,再采用Cytoscape3.9.0软件中的CytoHubba功能筛选出前十基因靶点。最后,通过Uniprot数据库、PDB数据库获取受体3D结构,通过AutoDock Vina 1.1.2进行分子对接,并用PyMOL 2.5软件将结果进行可视化呈现。结果从文献检索中获得梓木草β-谷甾醇、柯伊利素、木犀草素等9个成分,与炎症共有STAT3、ESR1、EGFR等51个共同靶点。GO富集分析和KEGG富集分析结果显示梓木草主要与RNA聚合酶Ⅱ启动子初始微RNA(pri-miRNA)转录的正向调节、炎症反应的负调节、RNA聚合酶Ⅱ启动子转录的负调节等生物过程和调控癌症的通路、化学致癌-受体活化、胰岛素抵抗等信号通路有关。分子对接结果显示有7个成分可与6NJS、1M17、2Q70等多个炎症蛋白结合。结论梓木草的抗炎作用可能通过多成分与多个炎症蛋白结合、多靶点调控多通路影响炎症反应。

Objective To explore the anti-inflammatory mechanisms of Lithospermum Zollinger DC based on network pharmacology and molecular docking.Methods This study,conducted from January to March 2023,initially utilized network pharmacology research methods to search for components of Lithospermum Zollinger DC in the literature,and the structural formulas and 3D structures of the components were obtained through the TCMSP and PubChem databases.The component structures were then imported into the Swiss Target Prediction database to obtain corresponding targets.Secondly,relevant targets for inflammation were retrieved from the DisGeNET and GeneCards databases,and common gene targets for Lithospermum Zollinger DC components and inflammation were identified using the Bioinformatics platform.A"Lithospermum Zollinger DC components-potential targets-inflammation"network was constructed using Cytoscape 3.9.0 software.Subsequently,the STRING database was utilized to obtain the Lithospermum Zollinger DC antiinflammatory protein-protein interaction(PPI)network,and the DAVID platform was employed for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.The top ten gene targets were screened using the CytoHubba function in Cytoscape 3.9.0 software.Finally,the 3D structure of the receptor was obtained through the Uniprot and PDB databases,molecular docking was performed using AutoDock Vina 1.1.2,and the results were visualized with PyMOL 2.5 software.Re⁃sults Nine components,includingβ-sitosterol,chrysoeriol,and luteolin,were identified from the literature search,with 51 common targets such as STAT3,ESR1,and EGFR.GO enrichment analysis and KEGG enrichment analysis showed that Lithospermum Zollinger DC is mainly associated with biological processes like positive regulation of pri-miRNA transcription from RNA polymeraseⅡpromot‑er,negative regulation of inflammatory response,negative regulation of transcription from RNA polymeraseⅡpromoter,and pathways in cancer,chemical carcinogenesis-receptor activation,and insulin resistance.Molecular docking results showed that seven components could bind to multiple inflammatory proteins such as 6NJS,1M17,2Q70,etc.Conclusion The anti-inflammatory effect of Litho⁃spermum Zollinger DC may be achieved by the combination of multiple components interacting with multiple inflammatory proteins and regulating multiple pathways to affect the inflammatory response.