基于网络药理学和分子对接技术探讨岑连口服液治疗病毒性呼吸道感染的作用机制

Based on Network Pharmacology and Molecular Docking to Explore the Mechanism of Action of Cenlian Oral Liquid in the Treatment of Viral Respiratory Tract Infections

摘要: 目的：利用网络药理学与分子对接技术探讨岑连口服液治疗病毒性呼吸道感染(VRTI)的主要活性成分、潜在作用靶点及机制。方法：本研究以网络药理学为基础，借助中药系统药理学数据库与分析平台(TCMSP)及PubMed等数据资源，分析岑连口服液中潜在的有效成分及其相应靶标；接着，通过GeneCards数据库和OMIM数据库检索VRTI相关的疾病靶点，并确定成分与疾病之间的共同靶点集合；接着，利用STRING数据库搜集蛋白质相互作用信息，并应用Cytoscape3.8.0软件绘制蛋白质-蛋白质相互作用(PPI)网络以及药物–成分–靶点关系图；再采用RStodio工具包进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集研究，以识别潜在的作用机制通路；最后，使用AutoDock软件对关键活性成分与核心靶点进行分子对接验证实验。结果：共筛选出岑连口服液141个活性成分、1900个成分靶点；VRTI相关的疾病靶点12491个，与岑连口服液的交集靶点共有243个；其中主要活性成分包括槲皮素(quercetin)、山柰酚(kaempferol)、木犀草素(luteolin)、汉黄芩素(wogonin)、异微凸剑叶莎醇(7-O-methylisomucronulatol)等，核心靶点包括肿瘤蛋白p53 (TP53)、JUN、雌激素受体1 (ESR1)、蛋白激酶B1 (AKT1)、热休克蛋白90α家族A类成员1 (HSP90AA1)、肿瘤坏死因子(TNF)等；涉及脂质与动脉粥样硬化(Lipid and atherosclerosis)、人类巨细胞病毒感染(Human cytomegalovirus infection)、PI3K-Akt信号通路(PI3K-Akt signaling pathway)等通路；分子对接结果显示，5个主要活性成分与关键靶点均有不同程度的对接效果，其中槲皮素对接效果最好，以氢键结合为主。结论：岑连口服液通过多成分、多靶点、多通路协同作用介导对VRTI的治疗效应，体现中药整体调节的药理特征。

Abstract: Objective: To explore the main active ingredients, potential therapeutic targets, and mechanisms of Cenlian Oral Liquid in the treatment of Viral Respiratory Tract Infections (VRTI) using network pharmacology and molecular docking techniques. Methods: Based on network pharmacology, potentially effective components and their corresponding targets in Cenlian Oral Liquid were analyzed using data resources such as the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and PubMed. Subsequently, VRTI-related disease targets were retrieved from the GeneCards and OMIM databases, and the intersection targets between the components and the disease were identified. Protein-Protein Interaction (PPI) information was collected using the STRING database, and Cytoscape 3.8.0 software was used to construct PPI networks and drug–component–target relationship diagrams. The RStudio toolkit was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to identify potential mechanism-related pathways. Finally, AutoDock software was used to perform molecular docking validation between key active components and core targets. Results: A total of 141 active components and 1900 component targets were identified in Cenlian Oral Liquid, and 12,491 VRTI-related disease targets were retrieved, with 243 overlapping targets between the two. The main active components included quercetin, kaempferol, luteolin, wogonin, and 7-O-methylisomucronulatol. The core targets included Tumor Protein p53 (TP53), JUN, Estrogen Receptor 1 (ESR1), protein kinase B1 (AKT1), Heat Shock Protein 90α family class A member 1 (HSP90AA1), and Tumor Necrosis Factor (TNF). The enriched pathways included lipid and atherosclerosis, human cytomegalovirus infection, and the PI3K-Akt signaling pathway. Molecular docking results indicated that the five main active components exhibited varying degrees of binding affinity with the key targets, with quercetin showing the best docking effect, mainly through hydrogen bonding. Conclusion: Cenlian Oral Liquid exerts its therapeutic effect on VRTI through the synergistic action of multiple components, multiple targets, and multiple pathways, reflecting the holistic regulatory pharmacological characteristics of traditional Chinese medicine.