基于网络药理学与分子对接探讨苍耳子散化裁方治疗鼻窦炎的作用机制

A study on the action mechanism of Cangerzi San on sinusitis based on network pharmacology and molecular docking technology

目的:基于网络药理学和分子对接探讨苍耳子散化裁方治疗鼻窦炎的作用机制。方法:通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选出方剂的药物成分及其对应的成分靶标,将UniProt数据库筛选的相关药物靶标和GeneCards、CTD数据库筛选的鼻窦炎疾病靶标取交集;运用STRING平台构建蛋白质-蛋白质相互作用网络;采用Metascape平台对靶标进行基因本体论(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析。利用Cytoscape 3.8.2软件构建药物-成分-靶标网络图,最后使用Autodock软件对关键靶标及化合物进行分子对接,选择最佳的结合靶标。结果:筛选出相关活性成分57个,成分靶标与疾病靶标相交得出217个靶标。其主要活性成分为槲皮素(Quercetin)、木犀草素(Luteolin)、β-谷甾醇(Beta-Sitosterol)、金合欢素(Acacetin)、柚皮素(Naringenin)、豆甾醇(Stigmasterol)、芦荟大黄素(Aloe-emodin)等。其核心基因为丝氨酸/苏氨酸蛋白激酶1(Serine/threonine Protein Kinase 1,AKT1)、肿瘤蛋白p53(Tumor Protein p53,TP53)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3,CASP3)等。在分子对接中,其主要活性成分与关键靶标对接结果的能量均低于-5 kcal/mol。结论:通过网络药理学和分子对接研究了苍耳子散化裁方治疗鼻窦炎的潜在有效成分和作用机制,为今后进一步的机制研究与实验设计提供了依据。

Objective:Based on network pharmacology and molecular docking technology,the action mechanism of Cangerzi San(苍耳子散)on sinusitis was investigated.Methods:The medicine components of the prescriptions and their corresponding component targets were screened by TCMSP database.The relevant medicine targets screened by UniProt database and the sinusitis disease targets screened by GeneCards and CTD databases were intersected.The STRING platform was used to construct a PPI network.Metascape platform was used to perform a GO enrichment analysis and a KEGG pathway enrichment analysis on the targets.Cytoscape 3.8.2 software was used to construct a medicine-component-target network diagram.Finally,Autodock software was used to carry out molecular docking of key targets and compounds,and the the best binding targets were selected.Results:57 relevant active ingredients were screened out and 217 targets were obtained by the intersection of component targets and disease targets.The main ingredients were quercetin,luteolin,β-sitosterol,acacetin,naringenin,stigmasterol,aloe-emodin,etc..The core genes were AKT1,TP53,TNF,IL-6,CASP3,etc..The energy of the molecular docking results of the main active ingredients and key targets were all lower than-5 kcal/mol.Conclusion:The potential active ingredients and action mechanism of Cangerzi San on sinusitis are studied through network pharmacology and molecular docking,it provides a basis for further mechanism research and experimental design in the future.