摘要
目的基于网络药理学探讨钩藤治疗肝恶性肿瘤的潜在作用机制。方法利用TCMSP、Pubchem数据库查阅钩藤主要活性成分与结构,通过Swiss Target Prediction数据库预测钩藤活性成分作用的人类靶点。应用GeneCards、OMIM和DisGeNET数据库获取肝恶性肿瘤靶点并与药物靶点映射,使用Cytoscape软件构建“钩藤活性成分-靶点-肝恶性肿瘤”网络,对药物疾病共同靶点使用DAVID数据库进行GO及KEGG通路富集分析,并对结果进行可视化呈现。采用Autodock Vina软件预测关键活性成分与靶点的结合能,利用PyMOL软件对结果进行可视化处理。最后在KM-plotter数据库绘制关键作用靶点的Kaplan-Meier曲线。结果检索得到钩藤主要活性成分为槲皮素、山奈酚、长春苷内酰胺_qt等28种,与肝恶性肿瘤交互共同靶点324个,其中SRC、PIK3R1、AKT1等靶点为关键作用靶点。KEGG分析筛选出钩藤主要通过癌症途径、EGFR酪氨酸激酶抑制剂耐药、前列腺癌等信号通路发挥抗肝恶性肿瘤作用。分子对接提示钩藤前10名的活性成分与核心靶点之间均存在较强的对接活性。生存分析结果显示,SRC、PIK3R1、STAT3、ESR1等基因表达差异对肝癌患者5年总生存率影响具有统计学意义(P<0.05)。结论初步揭示了钩藤活性成分通过作用于多靶点,参与多途径发挥抗肝恶性肿瘤作用,为肝恶性肿瘤的治疗提供了新的思路和理论依据。
Objective To explore the potential mechanism of action of Uncaria in treating malignant tumor of liver based on network pharmacology.Methods TCMSP and Pubchem databases were used to review the main active ingredients and structures of Uncaria,and the Swiss Target Prediction database was used to predict the human targets of Uncaria.GeneCards,OMIM,and DisGeNET databases were used to obtain targets of liver malignant tumors,which were mapped with drug targets.Cytoscape software was used to construct the"Active ingredients of Uncaria-targets-liver malignant tumor"network,and the DAVID database was used to perform GO and KEGG pathway enrichment analyses on drug-disease co-targets and visualize the results.Autodock Vina software was used to predict the binding energy of the key active ingredients to the targets,and the results were visualized using PyMOL software.Kaplan-Meier curves of key targets were plotted using the KM-plotter database.Results 28 main active ingredients of Uncaria,including quercetin,kaempferol,and vincosidelactam_qt were retrieved,and 324 common targets interacting with malignant tumor of liver,among which SRC,PIK3R1,and AKT1 were the key targets.KEGG analysis screened that Uncaria mainly exerted its anti-malignant tumor of liver effect on the signaling pathway of pathways in cancer,EGFR tyrosine kinase inhibitor resistance,and prostate cancer.The molecular docking showed that there was strong docking activity between the first 10 active ingredients of Uncaria and the core targets.The survival analysis showed that the differences in gene expression of SRC,PIK3R1,STAT3 and ESR1 had a statistically significant effect on the 5-year overall survival rate of the patients of malignant tumor of liver.Conclusions This study preliminarily reveals that the active ingredients of Uncaria exert anti-malignant tumor of liver effects by acting on multiple targets and participating in multiple pathways,providing new ideas and theoretical basis for the treatment of malignant tumor of liver.
作者
申超赞
刘力华
杨章宏
陈亮
罗满云
李洋全
谢江
龙文明
邱敏
Shen Chaozan;Liu Lihua;Yang Zhanghong;Chen Liang;Luo Manyun;Li Yangquan;Xie Jiang;Long Wenming;Qiu Min(The Second People's Hospital of Huaihua,Huaihua,Hunan 418400,China)
出处
《齐齐哈尔医学院学报》
2025年第5期422-430,共9页
Journal of Qiqihar Medical University
基金
湖南中医药管理局科研课题(D2024072)
湖南省卫生健康委科研课题(202213014496)。
关键词
网络药理学
分子对接
钩藤
肝恶性肿瘤
Network pharmacology
Molecular docking
Uncaria
Malignant tumor of liver
