基于网络药理学和分子对接探讨桃仁红花煎治疗心律失常的作用机制

Exploring the Mechanism of Action of Taoren Honghua Decoction in the Treatment of Cardiac Arrhythmias Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学和分子对接的方法探讨桃仁红花煎治疗心律失常的有效成分、作用靶点及其作用机制。方法：通过TCMSP、TCM-ID筛选桃仁红花煎的有效成分并预测其作用靶点，对成分–靶点网络拓扑分析后得到主要有效成分。在GeenCards、DisGeNET、Drugbank及TTD数据库获得心律失常靶点，对交集靶点进行蛋白蛋白相互作用(PPI)筛选出关键靶点，并进行基因本体论(GO)和京都基因与基因百科全书(KEGG)富集参与的生物学过程及信号通路，最后通过分子对接验证成分与靶点的结合程度。结果：筛选出中药主要成分为Lactiflorin、(2R,3R)-4-methoxyl-distylin、Gibberellin A19、Gibberellin A30、Gibberellin A54、Gibberellin A60、Fumaricine、13-methylpalmatrubine、N-methyllaurotetanine；关键靶点为RHOA、EGFR、SRC、STAT3、RAC1、FYN。KEGG表明钙信号通路、cAMP等信号通路在治疗心律失常中发挥主要作用，分子对接结果提示中药成分能够与关键靶点稳定结合。结论：桃仁红花煎治疗心律失常的分子机制较为复杂，本研究为进一步揭示其药理作用提供了新的思路。

Abstract: Objective: To investigate the active ingredients, action targets and their mechanisms of action of Taoren Honghua decoction in the treatment of cardiac arrhythmias based on network pharmacolo-gy and molecular docking methods. Methods: The active ingredients of Taoren Honghua decoction were screened by TCMSP and TCM-ID and their targets of action were predicted, and the main active ingredients were obtained after topological analysis of the ingredient-target network. Arrhythmia targets were obtained in GeenCards, DisGeNET, Drugbank and TTD databases, protein-protein in-teractions (PPI) were performed on the intersecting targets to screen out the key targets, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to enrich the biological processes and signaling pathways involved, and finally the degree of binding of the com-ponents to the targets was verified by molecular docking. Results: The main components of the Chinese medicine were screened as Lactiflorin, (2R,3R)-4-methoxyl-distylin, Gibberellin A19, Gib-berellin A30, Gibberellin A54, Gibberellin A60, Fumaricine, 13-methylpalmatrubine, N-methyllaurotetanine; the key targets were RHOA, EGFR, SRC, STAT3, RAC1, FYN. KEGG indicated that calcium signaling pathways, cAMP and other signaling pathways play a major role in the treatment of cardiac arrhythmias, and the molecular docking results suggest that the herbal com-ponents can bind to the key targets stably. Conclusion: The molecular mechanism of Taoren Honghua decoction in the treatment of cardiac arrhythmias is complex, and this study provides a new idea to further reveal its pharmacological effects.