基于网络药理-分子对接研究地格达治疗酒精性肝病的“类药同治”作用机制

A study on the mechanism of Digeda in the treatment of alcoholic liver disease based on network pharmacology and molecular docking technology

目的利用网络药理学和分子对接技术预测“地格达”类药物治疗酒精性肝病(ALD)的作用机制。方法选取“地格达”类药物的25个化学成分为研究对象,利用中药系统药理学数据库与分析平台(TCMSP)数据库获取药物靶点;在DrugBank、PharmGKB、GeneCards和TTD数据库收集ALD疾病靶点并与“地格达”类药物靶点进行交集;运用STRING数据库和Cytoscape软件构建蛋白互相作用网络模型;采用Metascape数据库进行GO功能注释和KEGG通路分析;使用Autodock软件进行分子对接。结果通过各数据库检索得到“地格达”类19个药物的24个化合物(其中排除1个无靶点信息的化合物)的149个相关靶点、收集到ALD疾病相关靶点1593个,交集得出“地格达”类药物治疗ALD的靶点62个,KEGG通路分析结果显示共有219条通路与治疗ALD密切相关。分子对接结果显示分子与靶点蛋白的结合能均为负数,有较高的亲和力,与网络药理预测结果相符。结论本研究从网络药理学的角度为“地格达”类药物治疗ALD的活性成分和作用机制的深入研究提供了依据和思路。

Objective To predict the mechanism of Digeda in the treatment of alcoholic liver disease(ALD)using network pharmacology and molecular docking technology.Methods A total of 25 chemical components of Digeda were selected for the study,and the action targets of Digeda were obtained through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).ALD targets were collected from DrugBank,PharmGKB,GeneCards and therapeutic target database(TTD)for intersection with the action targets of Digeda.STRING database and Cytoscape software were used to construct protein interaction network models.Metascape database was used for gene ontology(GO)function annotation and Kyoto encyclopedia of genes and genomes(KEGG)-based pathway analysis.Autodock software was used for molecular docking.Results 149 related targets of 24 compounds from 19 Digeda drugs(including one compound with no target information)and 1593 ALD-related targets were collected by retrieving the above-mentioned databases.62 ALD-Digeda intersection targets were obtained through intersection analysis,and the results of KEGG pathway analysis showed that a total of 219 pathways were involved in the treatment of ALD.The molecular docking results showed that the binding energy of the molecules to the target proteins was all negative and had high affinity,which was consistent with the predicted results of network pharmacology.Conclusion This study provides a basis and ideas for the in-depth study of the active ingredients and mechanism of Digeda in the treatment of ALD from the perspective of network pharmacology.