基于网络药理学的当归抗碳离子辐射机制研究

Study on the Mechanism for Danggui Anti-carbon Ion Radiation Based on Network Pharmacology

基于网络药理学技术探讨当归抗碳辐射的可能机理。利用中药系统药理学数据库与分析平台和文献挖掘获取当归活性成分及其作用靶点,利用GeneCard数据库获取碳离子辐射靶点,活性成分靶点与碳离子辐射靶点的交集靶点为当归抗碳离子辐射的潜在靶点;构建活性成分-潜在靶点网络;对潜在靶点进行功能富集和通路富集分析;构建潜在靶点的蛋白质相互作用网络,获得核心靶点;将核心靶标与活性成分进行分子对接,以验证网络药理学的结果。共获得9个活性成分和98个抗碳离子辐射的潜在靶点;当归抗辐射作用的主要活性成分是阿魏酸、藁本内酯、谷甾醇和豆甾醇;功能富集分析显示,潜在靶点主要参与细胞应激反应、炎症反应、激酶活性等生物过程,以及DNA结合、激酶结合、核受体活性等分子功能;通路富集分析显示,潜在靶点主要参与PI3K-Akt、MAPK等多条相互作用的信号通路;蛋白质相互作用分析显示,VEGFA、EGFR、CTNNB1等靶点为当归抗碳离子辐射的核心靶点;分子对接表明活性成分与核心靶点具有良好的结合能力。本研究结果表明,当归主要通过调节炎症反应、免疫反应、细胞凋亡与存活以及损伤修复等发挥抗碳离子辐射作用。

To study the possible mechanism of Danggui anti-carbon ion radiation based on network pharmacology.The Danggui active ingredients and the targets were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature mining.Carbon ion radiation targets were obtained from GeneCard database.The intersection targets of the active ingredient targets and the carbon ion radiation targets were the potential targets for Danggui anti-carbon ion radiation.Active ingredients-potential targets network was constructed.Functional enrichment and pathway enrichment analysis of potential targets were performed.The protein-protein interaction(PPI)network of the potential targets was constructed and the the hub targets were obtained.Molecular docking between the hub targets and active ingredients was performed to verify the results of network pharmacology.A total of nine Danggui active ingredients and ninety-eight potential targets of Danggui anti-carbon ion radiation were obtained.The main active ingredients of Danggui anti-carbon ion radiation were ferulic acid,ligustilide,sitosterol and stigmasterol.Functional enrichment analysis showed that potential targets were primarily engaged in biological processes such as cellular stress response,inflammatory response,kinase activity,as well as molecular functions such as DNA binding,kinase binding,and nuclear receptor activity.Pathway enrichment analysis showed potential targets were mainly involved in PI3K-Akt signaling pathway,MAPK signaling pathway,etc,which interact with each other.PPI network showed that VEGFA,EGFR,CTNNB1,etc.were the hub targets of Danggui anti-carbon ion radiation.The molecular docking results showed that the active ingredient has a good binding activity to the hub targets.This study indicated that Danggui anti-carbon ion radiation was mainly through regulating inflammatory reaction,immune response,cell apoptosis and survival,and damage repair.