敦煌医方大泻肺汤对肺炎的体外活性及其作用机制的化学生物信息学分析

Analysis of in Vitro Activity and Mechanism of Dunhuang Yifang Daxiefei Decoction on Pneumonia Based on Chemical Bioinformatics

关键词:  敦煌医方  大泻肺汤  肺炎  复杂网络分析  化学生物信息学  作用机制

Key words:  Dunhuang prescription  Daxiefei decoction  pneumonia  complex network analysis  chemical bioinformatics method  mechanism

摘要:

目的 利用化学生物信息学探讨敦煌医方大泻肺汤防治肺炎的有效性、作用机制及功效组配伍特点。方法 通过细胞实验研究大泻肺汤冻干粉溶液对肺上皮细胞增殖活性的影响。根据药味功效将方子分为清热、化痰、养阴3个功效组。利用TCMSP数据库和文献检索获取大泻肺汤化学成分，并在Swiss Target Prediction数据库预测其作用靶点。借助DrugBank、TTD、Genecards及DisGeNET数据库检索肺炎疾病靶点。采用STRING数据库和Cytoscape构建交集靶点互作网络和“药味-成分-靶点-通路”网络，DAVID数据库进行KEGG通路富集分析，分析功效分组配伍规律的科学内涵。利用Schr?dinger软件进行分子对接评估靶点-化合物亲和力，分子动力学模拟探究动态分子机制。结果 细胞实验显示大泻肺汤能够维持肺上皮细胞增殖、逆转LPS诱导的肺上皮细胞线粒体活性降低和减少细胞凋亡。复杂网络分析结果显示大泻肺汤3个功效组富集的通路主要分布于炎症调节和降低气道黏液高分泌2个模块，各模块间通过共有靶标基因联结又各有侧重。分子对接结果显示化合物槲皮素、黄芩素、异鼠李素等可能是大泻肺汤起效的多靶点成分，SRC、EGFR、PPARA等靶点与各个潜在活性化合物之间的亲和力较好，可能是大泻肺汤防治肺炎的潜在作用靶点。分子动力学模拟结果显示潜在活性化合物槲皮素与其靶蛋白SRC形成了稳定的分子间作用。结论 本研究初步揭示了大泻肺汤防治肺炎的物质基础和分子机制，并探讨了大泻肺汤不同功效组协同防治肺炎的科学内涵，为其现代化开发和临床推广提供化学生物信息学参考。

Abstract:

OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.