摘要
目的:基于网络药理学和分子对接技术探讨金银花抗肺纤维化的作用机制。方法:基于前期金银花代谢谱鉴定的活性成分和相关文献报道的成分,采用口服生物利用度(OB)≥30%,类药性(DL)≥0.18为阈值,借助TCMSP和SwissTargetPrediction数据库检索成分靶点;以“pulmonary fibrosis”“lung paralysis”“lung flaccidity”为关键词,通过GeneCards、TTD等数据库检索与肺纤维化相关的疾病靶点,绘制药物—疾病共有靶点韦恩图。利用STRING构建蛋白互作PPI网络,拓扑分析筛选核心靶点。运用Metascape对核心靶点进行GO功能分析和KEGG通路富集分析;并应用Cytoscape 3.7.1构建“金银花—成分—靶点—通路”网络;最后通过AutoDock_Vina将活性成分与核心靶点进行分子对接,验证结合力。结果:筛选得到24个潜在活性成分,挖掘436个成分靶点和364个疾病靶点,其中交集靶点93个,核心靶点有TP53、AKT1、MAPK1、STAT3等共17个。GO和KEGG分析发现金银花可能通过作用于病毒感染、癌症中的信号通路等关键信号通路来调控炎症反应和防御应答等。“金银花—成分—靶点—通路”网络图筛选核心化合物4个:木犀草素、槲皮素、山柰酚和金圣草素。分子对接进一步验证核心成分和关键靶点的相互作用,表明活性成分与其靶点有较好的对接活性。结论:网络药理学联用分子对接技术揭示金银花可以通过多成分、多通路、多靶点作用于肺纤维化,为其进一步的深入研究与临床应用提供了理论依据与新思路。
Objective:To explore the molecular mechanism of Lonicerae Japonicae Flos against pulmonary fibrosis based on network pharmacology and molecular docking technology.Methods:Based on the active ingredients identified by the metabolic profiles of Lonicerae Japonicae Flos and those reported in the literatures,the oral bioavailability(OB)≥30%and the drug-like property(DL)≥0.18 were used as the threshold,and the component targets were searched by TCMSP and SwissTargetPrediction databases.With“pulmonary fibrosis”,“lung paresis”and“lung flaccidity”as the keywords,the disease targets related to anti-pulmonary fibrosis were retrieved through GeneCards,TTD and other databases,and the Venn diagram of drug-disease common targets was drawn.Protein-protein interaction(PPI)network was constructed by STRING database,and core targets were screened by topological analysis.Then the Metascape was used for GO function analysis and KEGG pathway enrichment analysis of core targets.The“Lonicerae Japonicae Flos-component-target-pathway”network was constructed by using Cytoscape 3.7.1.Finally,through AutoDock_Vina connects the active ingredients with the core target to verify the binding force.Results:24 potential active components were screened,436 component targets and 364 disease targets were identified,including 93 intersection targets and 17 core targets including TP53,AKT1,MAPK1 and STAT3 etc.GO and KEGG analysis found that Lonicerae Japonicae Flos may regulate inflammatory response and defense response through acting on key signal pathways in viral infection and cancer.The network diagram of“honeysuckle-component-target-pathway”screened four core compounds:luteolin,quercetin,kaempferol and chryseriol.Molecular docking further verifies the interaction between main components and key targets,indicating that the active components have good docking activity with their targets.Conclusion:The results show that the combination of network pharmacology and molecular docking technology reveals that honeysuckle can act o
作者
庞玉扬
姚桂娟
蔡芷辰
PANG Yuyang;YAO Guijuan;CAI Zhichen(Xuzhou City Hospital of TCM,Xuzhou City,Jiangsu Province 221000)
出处
《医学理论与实践》
2024年第11期1808-1812,1829,共6页
The Journal of Medical Theory and Practice
关键词
金银花
肺纤维化
网络药理学
分子对接
作用机制
Lonicerae Japonicae Flos
Pulmonary fibrosis
Network pharmacology
Molecular docking
Mechanism of action
