基于网络药理学与分子对接技术探讨延胡索-鹿衔草药对治疗癌症疼痛的作用机制  

Discussion on the mechanism of treating cancer pain with Yanhusuo-Luxiancao based on network pharmacology and molecular docking technology

作　　者：胡悦 姜庆辉 马宝柱[2] 迟文成[2] 姜家康[2] HU Yue

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第一医院,黑龙江哈尔滨150040

出　　处：《中医临床研究》2024年第1期9-18,共10页Clinical Journal Of Chinese Medicine

基　　金：黑龙江省自然科学基金面上项目(H201478);黑龙江省应用技术研究与开发计划项(201903ZDKL010A)。

摘　　要：目的:基于网络药理学与分子对接技术探讨延胡索-鹿衔草药对治疗癌症疼痛的作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)中分别检索延胡索、鹿衔草的成分及作用靶点,并对照UniPort蛋白数据库进行匹配、校正、筛选,获取药物的最终靶点,并将结果导入Cytoscape3.9.0构建药物-成分-靶点图。分别在GeneCards数据库和OMIM数据库筛选癌症疼痛的靶点。在Venny 2.1.0中,导入药物靶点与疾病靶点,绘制韦恩图,取得交集靶点。再将交集靶点通过STRING网站、Cytoscape3.9.0进行拓扑分析,筛选后构建蛋白质-蛋白质相互作用网络图。基于DAVID数据库、微生信平台对筛选后的核心靶点进行基因本体论(GO)与京都基因与基因组百科全书(KEGG)富集分析,并绘制作图。最后应用分子对接技术验证核心成分与靶点蛋白的结合能力。结果:通过查找、筛选获取药物成分共56个,其中延胡索49个,鹿衔草7个;药物靶点203个;疾病靶点6020个;交集靶点182个。按照度值获得药物有效成分为槲皮素、山柰酚、β-谷甾醇等,有效蛋白靶点为丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤抑制蛋白p53(Tumor Protein p53,TP53)、Jun原癌基因(Jun Proto-Oncogene,JUN)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素(Interleukin,IL)-6、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)等。在GO分析中,生物过程主要参与RNA聚合酶II启动子转录的正调控,转录的正调控(DNA模板),药物反应等240条过程;细胞组分主要参与核、质膜、细胞质等27条;分子功能主要参与结合蛋白、酶结合、相同蛋白结合等48条。KEGG富集分析中,靶点主要涉及癌症通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、癌症中的蛋白多糖、肿瘤坏死因子信号通路、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)信�Objective:To explore the mechanism of Yanhusuo(Rhizoma Corydalis)-Luxiancao(Herba Pyrolae)in the treatment of cancer pain based on network pharmacology and molecular docking technology.Methods:The components and target of rhizoma corydalis and vherba pyrolae were searched in TCMSP,and the final target of the drug was obtained by matching,correction and screening against UniPort protein database,and the results were imported into Cytoscape 3.9.0 to construct the drug-component-target map.O Cancer pain targets were screened from GeneCards database and OMIM database,respectively.In Venny 2.1.0,drug targets and disease targets are introduced.Venn diagrams were drawn to obtain intersection targets.Then,topology analysis was conducted on the intersection targets through String website and Cytoscape 3.9.0,and protein-protein interaction network map was constructed after screening.GO and KEGG enrichment analysis was performed for the screened core targets based on DAVID database and wechat bioinformatics platform,and graphs were drawn.Finally,molecular docking verification was carried out between the core target and the component.Results:A total of 56 drug components were obtained by searching and screening,including 49 of Yanhusuo and 7 of Luxiancao.With 203 drug targets,and 6020 disease targets.There are 182 intersection targets.The effective components were quercetin,kaempferol,β-sitosterol,and the effective protein targets were RAC-alpha AKT1,TP53,JUN,TNF,IL-6,EGFR,etc..In GO analysis,BP was mainly involved in 240 processes including positive regulation of transcription from RNA polymerase II promoter,positive regulation of transcription(DNA-templated)and response to drug.CC is mainly involved in 27 processes including nucleus,plasma membrane and cytoplasm.MF mainly participates in 48 processes including protein binding,enzyme binding and identical protein binding.In KEGG enrichment analysis,with 94 targets were mainly involved pathways in cancer,hepatitis B,PI3K-Akt signaling pathway,proteoglycans in cancer,chagas

关 键 词：延胡索 鹿衔草 癌症疼痛 网络药理学 分子对接 

分 类 号：R441.1[医药卫生—诊断学]