基于网络药理学和分子对接研究灯盏细辛抗衰老的作用机制

Study on the anti-aging mechanism of Erigeron breviscapus based on network pharmacology and molecular docking

为了研究灯盏细辛抗衰老的潜在作用机制,本研究检索灯盏细辛口服入血成分,通过STITCH、SwissTargetPrediction、TCMSP、HAGR数据库预测入血成分抗衰老靶点,应用DAVID和STRING平台分析抗衰老靶点生物学功能和通路,采用STRING平台和Cytoscape软件构建抗衰老靶点蛋白互作网络、入血成分-靶点网络,再用Discovery Studio软件对网络分析结果进行分子对接验证。结果检索到灯盏细辛口服入血成分30个,包括黄酮类成分13个,咖啡酰类成分11个,其他类成分6个,预测作用于37个衰老靶点,涉及复制性衰老、细胞衰老等生物过程和寿命调节、肿瘤调节等通路。网络分析表明,TP53、AKT1、RB1、HRAS、HDAC1、SIRT1是抗衰老关键靶点,黄酮类成分槲皮素、芹菜素、木犀草素、黄芩素、山柰酚、柚皮素等是抗衰老关键活性成分。分子对接显示,这些黄酮类成分与TP53、AKT1、HDAC1、SIRT1有很好的结合活性;此外,9个咖啡酰类成分与这4个靶点也有较好的结合活性;入血成分与靶点的结合形式主要是氢键、π键。本研究初步揭示黄酮类和咖啡酰类成分是灯盏细辛抗衰老的潜在活性成分,可能通过调控衰老和肿瘤等相关生物过程和通路而发挥抗衰老作用,研究结果为后续实验验证提供了思路。

To investigate the potential anti-aging mechanism of Erigeron breviscapus,the components that can be absorbed into blood after oral administration of E.breviscapus were collected,and the potential targets of these absorbed components for anti-aging were predicted via STITCH,SwissTargetPredictio,TCMSP and HAGR databases,biological function analysis and pathway analysis of the predicted potential targets for anti-aging were undertaken through the DAVID and STRING platforms,protein-protein interaction network and absorbed component-target network were constructed using STRING platform and Cytoscape software,then the results of network analysis were verified by molecular docking using Discovery Studio software.A total of 30 components orally absorbed from E.breviscapus were retrieved,including 13 flavonoids,11 caffeoyl quinic acids and six others,they may act on 37 aging-related targets,and these targets are involved in biological processes such as replicative senescence and cellular senescence and pathways including lifespan regulation and tumor regulation,and so on.Network analysis showed that TP53,AKT1,RB1,HRAS,HDAC1,SIRT1 are the vital anti-aging targets of E.breviscapus,and the flavonoids quercetin,apigenin,luteolin,baicalein,kaempferol,naringenin are important bioactive components for anti-aging.The molecular docking analysis verified that these flavonoids have good binding capacity with TP53,AKT1,HDAC1,SIRT1;in addition,nine caffeoyl quinic acids have good binding capacity with these four targets too;these absorbed components mainly binded to these four targets with hydrogen bonds andπbonds.This study preliminarily revealed that the flavonoids and caffeoyl quinic acids could be the potential active components of E.breviscapus for anti-aging,and could play an anti-aging effect by regulating biological processes and pathways associated with aging,tumors and others,the findings in this study offer ideas for subsequent experimental studies.