基于网络药理学探讨六君安胃方减少结肠癌化疗期间消化道不良反应的作用机制研究

目的通过网络药理学方法探讨六君安胃方减少结肠癌化疗期间消化道不良反应的作用机制。方法通过检索中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)对六君安胃方中六味中药的化学成分、作用靶点进行筛选,并在GeneCards、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man,OMIM)等相关数据库中筛选出"chemotherapy-induced nausea and vomiting(CINV)"、"chemotherapy-induced diarrhea(CID)"相关靶点。利用STRING和Cytoscape3.6.0构建PPI网络图并通过网络拓扑分析获得关键蛋白靶点;利用R软件ClusterProfiler进行GO及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路功能富集分析;利用AutoTools1.5.6进行有效化学成分与关键蛋白靶点的分子对接。结果六君安胃方中的中药有效化学成分共103个,潜在作用靶点406个,CINV、CID疾病相关作用靶点851个,通过PPI网络拓扑分析得到关键蛋白靶点,前5个分别为AKT1、MAPK3、MAPK1、MAPK8、JUN;GO富集结果显示,氧化应激反应、凋亡信号通路调节、膜筏、膜微区域、泛素样蛋白连接酶结合、蛋白质丝氨酸/苏氨酸激活酶活性等排名靠前;KEGG富集通路结果显示,PI3K-AKt信号通路、MAPK信号通路、TNF信号通路等信号通路为主要作用通路;分子对接显示党参中的木犀草素与AKT1结合性最好。结论六君安胃方可能通过调节AKT1、MAPK3、MAPK1等关键蛋白,干预PI3K-AKt等相关炎症信号通路来减少化疗期间消化道不良反应。

Network Pharmacology Study on Therapeutic Mechanism of Liujun Anwei Decoction in Reducing Gastrointestinal Adverse Reaction of Colon Cancer During Chemotherapy

Objective To explore the therapeutic mechanism of Liujun Anwei Decoction in reducing gastrointestinal adverse reaction of colon cancer during chemotherapy by using network pharmacology.Methods The components and target proteins in Liujun Anwei Decoction were screened out by TCMSP,and the targets for chemotherapy-induced nausea and vomiting(CINV)and chemotherapy-induced diarrhea(CID)were filtered and collected from the databases such as GeneCards and OMIM.The protein-protein interaction(PPI)network was constructed and analyzed by STRING and Cytoscape3.6.0,key protein targets were obtained after network topology structure analysis,GO molecular function enrichment analysis and KEGG pathway enrichment analysis were carried out through Cluster Profiler R software,and the molecular docking of effective chemical components with key protein targets was realized by AutoTools1.5.6.Results A total of 103 active compounds and 406 potential actions targets were obtained from Liujun Anwei Decoction.There were 851 action targets related with CINV and CID.PPI network topology structure analysis revealed the key protein targets,and the leading 5 targets were (AKT1,MAPK3,MAPK1,MAPK8,and JUN).GO molecular function enrichment analysis results showed that the leading molecular functions were oxidative stress response,regulation of apoptosis signaling pathway,membrane raft,membrane micro-region,ubiquitin like protein ligase binding,and protein serine/threonine activating enzyme activity.The results of KEGG pathway enrichment analysis showed that PI3 K-Akt signaling pathway,MAPK signaling pathway and TNF signaling pathway were the primary signaling pathways.Molecular docking results showed that the luteolin of the Radix Codonopsis had the strongest binding to AKT1.Conclusion Liujun Anwei Decoction may can reduce the adverse reaction of digestive tract during chemotherapy by regulating key proteins of AKT1,MAPK3,MAPK1 and by intervening related inflammatory signaling pathways such as PI3 K-Akt signaling pathway.