基于网络药理学和分子对接研究汉黄芩素联合绿原酸治疗咳嗽变异性哮喘的机制

Mechanism of the Combination of Wogonin and Chlorogenic Acid in the Treatment of Cough Variant Asthma Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学与分子对接研究葛琳仪教授治疗咳嗽常用药对黄芩、蒲公英的主要活性成分汉黄芩素与绿原酸治疗咳嗽变异性哮喘(CVA)的潜在分子机制。方法：利用SwissTargetPrediction、Super-PRED和SEA数据库筛选汉黄芩素和绿原酸的作用靶点，利用GenCards和OMIM数据库检索CVA作用靶点。取两者交集后构建“化合物–靶点–疾病”网络。构建蛋白质–蛋白质互作(PPI)网络筛选核心靶点。通过GO和KEGG富集分析，探索其作用的生物学途径和涉及的信号通路。通过分子对接验证黄芩素和绿原酸与核心靶点的结合能力，初步揭示其治疗CVA的机制。结果：检索得到汉黄芩素和绿原酸的作用靶点289个，CVA作用靶点1957个，交集靶点112个。PPI网络构建分析后筛选10个核心靶点：PTGS2、EGFR、PPARG、MMP9、HIF 1α、NFKB1、TLR4、CCND1、MMP2、CREB1。GO功能富集分析得到427个条目，KEGG通路富集分析获得127条信号通路，包括HIF-1信号通路、PI3K-Akt信号通路和IL-17信号通路等。分子对接表明各组合对接结合能均在−5.0 kcal/mol以下，表明汉黄芩素和绿原酸与核心靶点能较好地结合。结论：汉黄芩素联合绿原酸通过多靶点和多通路治疗CVA，为研究汉黄芩素和绿原酸治疗CVA提供理论基础。

Abstract: Objective: To investigate the potential molecular mechanism of the main active ingredients of the combination of Scutellaria and Dandelion, wogonin and chlorogenic acid from the clinical experience of Professor Ge Linyi in the treatment of cough variant asthma (CVA) based on network pharmacology and molecular docking. Method: SwissTarget Prediction, Super PRED, and SEA databases were used to screen the targets of wogonin and chlorogenic acid, and GenCards and OMIM databases were used to search for CVA targets. Construct a “compound-target-disease” network by taking the intersection of these two clusters of gene targets. Constructing protein-protein interaction (PPI) network to screen core targets. Explore the biological pathways and signaling pathways involved in its action through GO and KEGG enrichment analysis. By molecular docking, the binding ability of wogonin and chlorogenic acid to core targets was verified, and their mechanism for treating CVA was preliminarily revealed. Result: 289 targets of wogonin and chlorogenic acid, 1957 targets of CVA, and 112 intersecting targets were retrieved. After constructing and analyzing the PPI network, 10 core targets were screened: PTGS2, EGFR, PPARG, MMP9, HIF 1α, NFKB1, TLR4, CCND1, MMP2, CREB1. GO functional enrichment analysis yielded 427 entries, while KEGG pathway enrichment analysis yielded 127 signaling pathways, including HIF-1 signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. Molecular docking showed that the binding energies of each combination were all below −5.0 kcal/mol, indicating that wogonin and chlorogenic acid could bind well to the core target. Conclusion: The combination of wogonin and chlorogenic acid can treat CVA through multi-target and multi-pathway, providing a theoretical basis for the study of wogonin and chlorogenic acid in the treatment of CVA.