[关键词]
[摘要]
目的:运用网络药理学方法研究金银花干预心力衰竭的主要活性成分及潜在靶点,探讨金银花干预心力衰竭的作用机制。方法:利用TCMSP数据库检索关于金银花中的化合物,口服生物利用度(OB)≥30%和类药性(DL)≥0.18作为筛选金银花活性成分的标准。在Genecards数据库和OMIM数据库中输入关键词—“Heart Failure”,筛选心力衰竭相关靶点。将金银花作用的靶点与心力衰竭相关的靶点取交集,得到金银花干预心力衰竭的靶点。通过STRING数据库构建交集基因的蛋白互作网络(PPI),应用Cytoscape3.8.2软件分析PPI网络中核心靶点,然后进行基因GO功能和KEGG 通路富集分析,构建“成分-靶点-通路”网络。使用Autodock Vina 1.2.0、Discovery Studio 2021、PyMol 2.2进行分子对接,验证网络药理学分析结果。结果:检索TCMSP 数据库得到金银花的23个化学活性成分,共有213个与心力衰竭相关的作用靶点。经GO功能和KEGG 通路富集分析显示,金银花主要参与癌症通路、内分泌抵抗等多种生物途径,主要涉及PI3K-Akt信号通路、cAMP 信号通路、TNF信号通路等。通过构建“成分-靶点-通路”网络,显示金银花干预心力衰竭的主要成分是secologanicdibutylacetal_qt和dinethylsecologanoside,排名较高的靶点有AKT1、PIK3R1、PIK3CA。分子对接结果显示上述两种成分与AKT1和PIK3R1结合活性较好。结论:金银花的主要活性成分secologanicdibutylacetal_qt和dinethylsecologanoside可能是通过参与调节AKT1、PIK3R1基因,干预PI3K-Akt 、cAMP、TNF等信号通路实现多靶点、多通路干预心力衰竭。
[Key word]
[Abstract]
Objective: The main active components and potential targets of Lonicerae japonicae in the intervention of heart failure were studied by network pharmacology method, and the mechanism of action of Lonicerae japonicae in the intervention of heart failure was discussed. Methods: Using the TCMSP database to search for compounds in honeysuckle, oral bioavailability (OB) ≥ 30% and drug-like properties (DL) ≥ 0.18 were used as the criteria for screening the active components of Lonicerae japonicae. Enter the keyword "Heart Failure" in the Genecards database and the OMIM database to screen heart failure-related targets. The target of Lonicerae japonicae action and heart failure-related targets were intersected to obtain the target of Lonicerae japonicae intervening in heart failure. The protein interaction network (PPI) of intersecting genes was constructed through the STRING database, the core targets in the PPI network were analyzed by Cytoscape 3.8.2 software, and then the gene GO function and KEGG pathway enrichment analysis were performed to construct a “component-target-pathway” network. Molecular docking was performed using Autodock Vina 1.2.0, Discovery Studio 2021 and PyMol 2.2 to verify the results of network pharmacology analysis. Results: The TCMSP database was searched to obtain 23 active components of Lonicerae japonicae and 213 targets related to heart failure. The GO function and KEGG pathway enrichment analysis showed that Lonicerae japonicae is mainly involved in cancer pathways, endocrine resistance and other biological pathways, mainly involving PI3K-Akt signaling pathway, cAMP signaling pathway, TNF signaling pathway, etc. By constructing a “component-target-pathway” network, it is shown that the main components of Lonicerae japonicae interfering with heart failure are secologanicdibutylacetal_qt and dinethylsecologanoside, ranking higher targets are AKT1, PIK3R1, and PIK3CA. Molecular docking showed that secologanicdibutylacetal_qt and dinethylsecologanoside had better binding activities to AKT1 and PIK3R1. Conclusion: The main active components of Lonicerae japonica are secologanicdibutylacetal_qt and dinethylsecologanoside may be involved in the regulation of AKT1 and PIK3R1 genes and the intervention of PI3K-Akt, cAMP and TNF signaling pathways to achieve multi-target and multi-channel intervention of heart failure.
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[基金项目]
]内蒙古自治区自然科学(No.2020MS08109);内蒙古自治区卫生健康科技计划项目(No.202201196.202201209)