基于网络药理学探讨青蒿鳖甲汤及补中益气汤治疗癌性发热的“同病异治”分子作用机制

Network Pharmacology-based Discussion on Molecular Mechanism of"Different Treatment of the Same Disease"in the Treatment of Cancerous Fever by Qinghao Bijia Tang and Buzhong Yiqi Tang

目的:通过网络药理学原理探讨青蒿鳖甲汤及补中益气汤治疗癌性发热的“同病异治”潜在作用机制。方法:在中药系统药理学数据库平台检索青蒿鳖甲汤及补中益气汤的活性成分并预测其潜在靶点,借助Cytoscape 3.7.2软件构建药物成分与靶点之间的网络图;通过疾病相关数据库平台检索癌性发热的疾病靶点,利用Venny在线工具构建药物与疾病的关键靶点Venny图。基于STRING数据库构建PPI网络图,然后按dgree值进一步筛选核心靶点;运用DAVID数据库实现对于基因本体、京都基因及基因组百科全书通路富集的分析。结果:经过筛选得到青蒿鳖甲汤有效活性成分45个,潜在作用靶点140个;补中益气汤有效活性成分163个,潜在作用靶点127个。经疾病数据库获得癌性发热相关靶基因3440个,3组靶点映射出关键靶点102个,根据dgree≥44筛选到13个核心靶点。富集出141个生物过程及47条信号通路。结论:青蒿鳖甲汤与补中益气汤治疗癌性发热主要与正向调控一氧化氮生物合成、DNA转录、酶结合、平滑肌细胞增殖等141个生物过程有关。通过肿瘤坏死因子、丝裂原活化蛋白激酶、NOD样受体、TOLL样受体、叉头转录因子等特异性通路调控癌症患者炎症水平,改善发热症状。

Objective:To explore the potential mechanism of"different treatment of the same disease"in the treatment of cancerous fever by Qinghao Bijia Tang and Buzhong Yiqi Tang through network pharmacology.Methods:The active ingredients of Qinghao Bijia Tang and Buzhong Yiqi Tang were searched from TCMSP,to predict the potential targets,the network plot between the drug components and the target sites were constructed via Cytoscape 3.7.2 software;disease targets of cancerous fever were retrieved from disease-related database platform,Venny diagram of key targets of disease and drugs were built using Venny online tool.PPI network diagram between proteins were constructed based on STRING database,and then the core targets were further screened according to Dgree value;GO and KEGG analysis were realized using DAVID database.Results:By screening,there were 45 active ingredients in Qinghao Biejia Tang,and 140 potential targets;163 active ingredients in Buzhong Yiqi Tang and 127 potential targets.All 3440 target genes related to cancerous fever were obtained through the disease database,three groups of targets mapped out of 102 key targets,and 13 core targets were screened according to Degree≥44.All 141 biological processes and 47 signal pathways were enriched.Conclusion:The treatment of cancerous fever with Qinghao Bijia Tang and Buzhong Yiqi Tang is mainly related to 141 biological processes such as positive regulation of nitric oxide biosynthesis,DNA transcription,enzyme binding,and smooth muscle cell proliferation.The therapy could adjust the patients’inflammation level and improve fever symptoms through specific pathways including TNF signal pathway,MAPK signal pathway,NOD-like receptor signal pathway,TOLL-like receptor signal pathway,and FOXO signal pathway.