摘要
目的:基于网络药理学和分子对接技术分析金银花抗甲型H1N1流感的有效活性成分,预测其作用靶点,并探讨潜在机制。方法:应用TCMSP数据库收集金银花的活性成分,并通过文献调研补充潜在活性成分;通过TCMSP及SwissTargetPrediction工具预测成分作用靶点,并与H1N1流感相关靶点进行映射;采用STRING数据库对靶点进行KEGG通路富集分析,并通过Cytoscape软件构建"药物-活性成分-靶点-通路"(H-C-T-P)网络,将靶点进行蛋白-蛋白互作(PPI)网络分析,得出金银花抗流感核心靶点;最后通过分子对接验证关键成分与核心靶点的结合活性。结果:共获得34个潜在活性成分,通过反向预测靶点,获得374个成分靶标,与679个H1N1流感相关靶标映射,共获得32个金银花抗流感的潜在作用靶点,利用这些靶标富集得到多种KEGG通路。H-C-T-P网络分析得出槲皮素、木犀草素、山奈酚、β-胡萝卜素和β-谷甾醇等成分可能是金银花抗流感的主要活性成分。结合PPI网络分析,认为JUN,MAPK14,MMP9和EGFR等靶点可能是金银花抗流感的主要作用靶点。将槲皮素与该靶点进行分子对接,发现同时满足空间匹配和能量匹配。结论:金银花可能是通过其活性成分调控IL-17、MAPK和松弛素等信号通路,干预细胞代谢的多个过程,抑制促炎因子的表达,发挥抗H1N1流感的作用,体现了中药多成分-多靶点-多通路的作用特点,该研究为深入阐释金银花抗甲型流感分子机制及进一步开发应用提供了参考。
Objective: Based on network pharmacology and molecular docking techniques,the effective active constituents of honeysuckle against H1N1 influenza A were analyzed.The targets and underlying mechanisms were explored.Methods: The TCMSP database and literature researches were used to collect the active constituents of honeysuckle.The targets of the components were predicted by TCMSP and SwissTargetPrediction tool,and mapped to the influenza-related targets.The enrichment of KEGG pathway was analyzed by STRING database,and the "herb-component-target-pathway"(H-C-T-P) network was constructed by Cytoscape.Then,the targets were analyzed by protein-protein interaction(PPI) network,and the core anti-influenza targets of honeysuckle were obtained.Finally,the binding activity of the key components to the core targets was verified by molecular docking.Results: A total of 34 potential anti-influenza components were obtained.Through reverse prediction of targets,374 component targets were obtained and mapped with 679 influenza-related targets,and a total of 32 potential antiinfluenza targets of honeysuckle were obtained.A variety of KEGG pathways were obtained from these targets.H-C-T-P network analysis shows that quercetin,luteolin,kaempferol,beta-carotene and beta-sitosterol may be the main active anti-influenza components of honeysuckle.Combined with PPI network analysis,it is considered that JUN,MAPK14,MMP9 and EGFR may be the main anti-influenza targets of honeysuckle.The quercetin was docked with the obtained targets,and it was found that both spatial matching and energy matching were satisfied.Conclusion: Honeysuckle may interfere with many processes of cell metabolism,inhibit the expression of proinflammatory factors and play an anti-influenza A H1N1 role by regulating IL-17,MAPK,and Relaxin signaling pathways.The results reflect the characteristics of multi-component-target-pathway of traditional Chinese medicine.This study provides a reference for the further interpreting the molecular mechanism of honeysuckle against
作者
高凯
宋延平
GAO Kai;SONG Yan-ping(Pharmacy College,Shaanxi University of Chinese Medicine,Xianyang 712046,China;Shaanxi Academy of Traditional Chinese Medicine,Xi'an 710003,China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2020年第23期2729-2737,共9页
Chinese Journal of New Drugs
关键词
金银花
甲型H1N1流感
网络药理学
分子对接
分子机制
honeysuckle
influenza A H1N1
network pharmacology
molecular docking
molecular mechanism
