基于网络药理学分析滋阴润目颗粒治疗干眼症的作用研究

Study on the Mechanism of Ziyin Runmu Keli in Treating Dry Eye Disease Based on Network Pharmacology

摘要: 目的：应用网络药理学和分子对接方法深入研究滋阴润目颗粒治疗干眼症(Dry Eye Disease, DED)的作用机制。方法：1) 利用TCMSP、Batman数据库收集滋阴润目颗粒的活性成分及相关靶点，通过Cytoscape 3.10.4软件进行可视化，利用GeneCards数据库获取并下载DED的高相关性靶点，借助venny 2.1在线平台绘制韦恩图得到交集靶点。2) 利用STRING数据库构建蛋白相互作用(PPI)网络，并用Cytoscape进行拓扑分析。利用R语言进行GO (Gene Ontology)功能和KEGG (Kyoto Encyclopedia of Genes and Genomes)通路富集分析并绘图。3) 使用AutoDockVina进行分子对接。结果：1) 共获得滋阴润目颗粒活性成分273个，对应靶点2066个，DED高相关性靶点1000个，得到337个交集靶点；2) PPI分析的结果显示AKT1、TP53为滋阴润目颗粒治疗DED的核心靶点，圆柚酮和2,4,7-三羟基-9,10-二氢菲为关键活性成分。GO与KEGG分析共得到3975条GO条目，203条KEGG通路。3) 分子对接结果表明2种核心活性成分与TP53和AKT1均有较好结合活性。结论：滋阴润目颗粒可能通过圆柚酮和2,4,7-三羟基-9,10-二氢菲等核心活性成分作用于TP53、AKT1等核心靶点治疗DED，为滋阴润目颗粒治疗DED的机制提供理论基础。

Abstract: Objective: To elucidate the underlying mechanism of Ziyin Runmu Keli in treating Dry Eye Disease (DED) using network pharmacology combined with molecular docking. Methods: 1) The active ingredients and related targets of Ziyin Runmu Keli were collected using the TCMSP and Batman databases, and visualized with Cytoscape 3.10.4 software. Highly relevant targets of dry eye disease (DED) were obtained and downloaded from the GeneCards database, and the intersection targets were identified by drawing a Venn diagram using the online platform Venny 2.1. 2) The protein-protein interaction (PPI) network was constructed via the STRING database, followed by topological analysis using Cytoscape. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed with R language, and the results were plotted. 3) Molecular docking was conducted using AutoDock Vina. Results: 1) A total of 273 active ingredients of Ziyin Runmu Granule were identified, corresponding to 2066 targets. Meanwhile, 1000 highly relevant targets of DED were obtained, and 337 intersection targets were finally determined. 2) PPI analysis revealed that AKT1 and TP53 were the core targets of Ziyin Runmu Granule in the treatment of DED, while nootkatone and 2,4,7-trihydroxy-9,10-dihydrophenanthrene were the key active ingredients. Additionally, 3975 GO terms and 203 KEGG pathways were enriched from GO and KEGG analyses. 3) Molecular docking results demonstrated that the two core active ingredients exhibited good binding activity with both TP53 and AKT1. Conclusion: Ziyin Runmu Keli may ameliorate DED through key active ingredients, such as nootkatone and 2,4,7-trihydroxy-9,10-dihydrophenanthrene, directly acting on core targets like TP53 and AKT1. This study provides a pharmacological and theoretical basis for the clinical application of Ziyin Runmu Keli in DED treatment.