基于网络药理学和分子对接技术预测升解通瘀汤治疗慢性心衰的分子机制

Prediction of Molecular Mechanism of Shengjie Tongyu Decoction in the Treatment of Chronic Heart Failure Based on Network Pharmacology and Molecular Docking Technology

目的采用网络药理学结合分子对接技术探讨升解通瘀汤治疗慢性心衰(CHF)的潜在分子作用机制。方法在TCMSP数据库、DrugBank数据库中筛选出升解通瘀汤的有效化学成分及其对应靶点;利用GeneCard、OMIM、TTD与DisGeNet数据库筛选CHF相关靶点;采用Cytoscape3.7.2软件构建"活性成分-靶点-疾病网络";应用STRING数据库构建候选靶点的蛋白互作网络,并运用MEODE软件对蛋白互作网络进行聚类;对聚类得到的核心模块进行GO与KEGG富集分析;最终对关键靶点与活性成分应用AutoDock Vina软件进行分子对接验证。结果最终有75个药物活性成分和109个基因被筛选出来作为升解通瘀汤治疗CHF的潜在活性成分与潜在靶点;活性成分主要为槲皮素、木犀草素、山柰酚、脱水淫羊藿素、异鼠李素、芒柄花黄素等黄酮类化合物;IL-6、MAPK1、MAPK8、AKT1、VEGFA、JUN是筛选出来的核心靶点;分子对接显示关键成分与靶点对接良好;GO富集分析显示升解通瘀汤可以通过参与包括血管生成、内皮细胞增殖的调节、细胞因子受体结合、凋亡信号通路的负调控、一氧化氮合酶活性的调节、活性氧代谢过程在内的多条生物学途径发挥作用;关键通路主要集中在Toll样受体信号通路、Nod样受体信号通路、MAPK信号通路、mTOR信号通路、jak-STAT信号通路、VEGF信号通路等通路上。结论本研究揭示了升解通瘀汤治疗CHF可能与其调节免疫炎症反应、细胞的增殖和凋亡、血管生成和氧化应激等多条生物学过程有关,为进一步深入研究其作用机制提供了理论基础和研究方向。

OBJECTIVE To explore the potential molecular mechanism of Shengjie Tongyu decoction in the treatment of chronic heart failure(CHF) by network pharmacology combined with molecular docking technique. METHODS The effective chemical constituents and their corresponding targets of Shengjie Tongyu decoction were screened from TCMSP database and DrugBank database. The related targets of chronic heart failure were screened by GeneCard, OMIM, TTD and DisGeNet databases. The "active components-targets-disease network" was constructed by Cytoscape3.7.2 software. The protein interaction network of candidate targets was constructed by STRING database, and the protein interaction network was clustered by MEODE software. The core modules obtained by clustering were enriched by GO and KEGG. Finally, the key targets and active components were verified by molecular docking with AutoDockVina software. RESULTS Seventy-five active components and 109 genes were screened out as the potential active components and potential targets of Shengjie Tongyu decoction in the treatment of CHF;the main active components were quercetin, luteolin, kaempferol, anhydroicaritin, isorhamnetin, formononetin and other flavonoids;IL-6, MAPK1, MAPK8, AKT1, VEGFA, JUN were the core targets. Molecular docking showed that the key components were well docked with the target,;GO enrichment analysis showed that Shengjie Tongyu decoction could play a role by participating in many biological pathways, including angiogenesis, regulation of endothelial cell proliferation, binding of cytokine receptors, negative regulation of apoptosis signal pathway, regulation of nitric oxide synthase activity and active oxygen metabolism. The key pathways are mainly concentrated in Toll-like receptor signal pathway, Nod-like receptor signal pathway, MAPK signal pathway, mTOR signal pathway, jak-STAT signal pathway, VEGF signal pathway and so on. CONCLUSION This study reveals that Shengjie Tongyu decoction in the treatment of chronic heart failure may be related to its regulation of immune inflammatory response, cell proliferation and apoptosis, angiogenesis and oxidative stress and other biological processes. it provides a theoretical basis and research direction for further study of its mechanism.