基于网络药理学及分子对接探讨骨碎补-补骨脂药对治疗骨转移癌痛的作用机制

Mechanism of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)Drug Pair on Treatment of Bone Metastasis Cancer Pain Based on Network Pharmacology and Molecular Docking

目的采用网络药理学及分子对接技术探讨骨碎补-补骨脂治疗骨转移癌痛的作用机制。方法通过文献查找、TCMSP数据库及BATMAN-TCM数据库获取骨碎补-补骨脂的活性成分及其对应的靶点,通过GeneCards数据库获得骨转移癌痛相关的靶点,利用Venn在线软件获取“化合物-疾病”共同靶点,运用Cytoscape 3.7.1软件构建“中药-化合物-靶点-疾病”网络图,使用STRING数据库绘制核心靶点PPI网络,利用DAVID对核心靶点进行GO功能及KEGG通路富集分析,最后使用Auto Dockt Vina对骨碎补-补骨脂关键化学成分与核心靶点进行分子对接验证。结果骨碎补-补骨脂关键化合物为豆甾醇、异补骨脂素、补骨脂酚、山柰酚、β-谷甾醇、木犀草素等,核心作用靶点涉及AKT1、TP53、IL-6等;GO生物学过程分析表明骨碎补-补骨脂活性成分的基因功能主要表现在RNA聚合酶Ⅱ启动子的正调控、信号转导、细胞增殖的正调控等过程,KEGG结果表明骨碎补-补骨脂主要作用与AKT1、TP53、IL-6等核心靶点和癌症通路等信号通路有关。分子对接结果表明豆甾醇、异补骨脂素、补骨脂酚、山柰酚、β-谷甾醇、木犀草素与AKT1、TP53、IL-6有很好的结合能力。结论骨碎补-补骨脂活性成分豆甾醇、异补骨脂素、补骨脂酚、山柰酚、β-谷甾醇、木犀草素可能通过癌症通路等信号通路作用于AKT1、TP53、IL-6等关键靶点而发挥治疗骨转移癌痛的功效。

Objective To use network pharmacology and molecular docking technology to explore the mechanism of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)for the treatment of bone metastasis cancer pain.Methods Through literature search,TCMSP database and BATMAN-TCM database,the active ingredients of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)and their corresponding targets were obtained,the targets related to bone metastasis cancer pain were obtained through GeneCards database,and the"compound-disease"common targets were obtained by using Venn online software.Cytoscape 3.7.1 software was used to construct“Chinese medicine-compound-target-disease”network diagram,STRING database was used to draw core target PPI network,DAVID was used to perform GO function and KEGG pathway enrichment of core target.Auto Dockt Vina was used to verify the molecular docking between the key chemical components of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)and their core target.Results The key compounds of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)were stigmasterol,isopsoralen,bakuchiol,kaempferol,β-sitosterol,luteolin,etc.The core targets involved AKT1,TP53,IL-6,etc.GO biological process analysis showed that the gene function of the active ingredients of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)was mainly manifested in the positive regulation of RNA polymerase II promoter,signal transduction,and positive regulation of cell proliferation.The results of KEGG showed the main role of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)was related to AKT1,TP53,IL-6 and other core targets and cancer signaling pathways.The molecular docking results showed that stigmasterol,isopsoralen,bakuchiol,kaempferol,β-sitosterol,luteolin had good binding ability with AKT1,TP53,and IL-6.Conclusion Active ingredients stigmasterol,isopsoralen,bakuchiol,kaempferol,β-sitosterol,luteolin of Gusuibu(Drynariae Rhizoma)-Buguzhi(Psoraleae Fructus)may act on AKT1,TP53,IL-6 and other key targets through signaling pathways such as cancer pathway to treat bone metastasis cancer pain.