摘要
目的基于网络药理学分析清营汤治疗乳腺癌化疗后皮肤黏膜毒性反应(mucocutaneous toxicity,MT)的关键化合物及其作用靶点通路,以探索其治疗作用的分子机制。方法通过中药系统药理学数据库分析平台、中医药综合数据库等在线数据库和文献检索筛选水牛角、生地黄、金银花、连翘、丹参、黄连、玄参、竹叶、麦冬的有效成分,并在SwissTargetPrediction数据库预测有效成分靶点,从OMIM与Gene Cards数据库获取MT的相关疾病靶点,将药物靶点与疾病靶点通过Venny2.1平台网站确认共同作用靶点。将共同作用靶点利用String和Cytoscape软件进行蛋白质-蛋白质相互作用(proteinprotein interaction,PPI)网络构建及关键靶点筛选,对关键靶点进行基因本体论(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,最后通过使用Autodock Dock将关键靶点与药物有效成分进行分子对接验证及可视化处理。结果筛选出清营汤的167个有效成分,并可作用于1034个靶点,与MT相关的分子靶点有1141个,药物-疾病交集靶点154个,其中,前5位有效成分槲皮素、木犀草素、山奈酚、牛蒡子苷甲醚、β-谷固醇发挥了重要作用。PPI分析结果显示,关键靶点为STAT3、PIK3CA、PIK3R1、CTNNB1、HRAS。GO功能富集分析结果显示清营汤有效成分主要影响蛋白激酶活性、丝裂原活化蛋白激酶级联的正调控等;KEGG通路富集分析结果显示,清营汤有效成分主要涉及丝裂原活化蛋白激酶(mitogenactivated protein kinase,MAPK)信号通路、磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K)-蛋白激酶B(protein kinase B,PKB)信号通路、白细胞介素(interleukin,IL)-17信号通路等。分子对接结果显示清营汤木犀草素、β-谷固醇、牛蒡子苷甲醚与关键靶点的最小结合能均小于﹣5kcal/mol,具有较好的结合活性,槲皮素、山奈酚与关�
Objective To analyze the key compounds and target pathways of Qingying decoction in the treatment of chemotherapy-induced mucocutaneous toxicity(MT)of breast cancer based on network pharmacology,and to explore the molecular mechanism of Qingying decoction.Method The active ingredients of ox horn,rehmanniae radix,lonicera japonica,fructus,salvia miltiorrhiza,rhizoma coptidis,scrophularia radix,bamboo leaf and Ophiopogonis Radix were identified through database screening using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID)and other relevant online resources as well as a comprehensive literature search,and the potential targets were predicted in SwissTargetPrediction database.The disease targets related to MT were obtained from OMIM and Gene Cards databases,and the intersection of drug targets and disease targets was performed to screen out the common targets.The protein-protein interaction(PPI)network was constructed and key targets were screened by String and Cytoscape software.Gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the key targets.AutoDock was used to verify and visualize the molecular docking between the key targets and the active components of the drug.Result A total of 167 active ingredients of Qingying decoction were screened,which could act on 1034 targets,including 1141 molecular targets related to MT and 154 drug-disease intersection targets,among which the top five active components of quercetin,luteolin,kaempferol,arctigenin methyl ether andβ-sitosterol played an important role.PPI analysis showed that the top five key targets with degree value were STAT3,PIK3CA,PIK3R1,CTNNB1 and HRAS.GO functional enrichment analysis showed that the active ingredients of Qingying decoction mainly affected protein kinase activity and the positive regulation of mitogen-activated protein kinase cascade.KEGG pathway enric
作者
刘苏燕
孙红
Liu Suyan;Sun Hong(Fujian University of Traditional Chinese Medicine,Fujian Fuzhou 350122,China)
出处
《创伤与急诊电子杂志》
2024年第3期192-202,211,共12页
Journal of Trauma and Emergency(Electronic Version)
基金
福建省自然科学基金项目(2022J011004)
福建省卫生健康科技计划项目(2022CXB001)。
关键词
清营汤
皮肤黏膜毒性反应
网络药理学
Qingying decoction
Mucocutaneous toxicity
Network pharmacology
