基于网络药理学和分子对接探讨黄芪甲苷、木香烃内酯的抗乳腺癌机制  

Discussion on anti-breast cancer mechanism of astragaloside Ⅳ and costunolide based on network pharmacology and molecular docking

作　　者：罗娇 熊书[1] 马强[1] 李国利[1] 孙厚良[1] 张时恒 张冬梅 LUO Jiao;XIONG Shu;MA Qiang;LI Guoli;SUN Houliang;ZHANG Shiheng;ZHANG Dongmei(Chongqing Three Gorges Medical College,Chongqing 404120,China)

机构地区：[1]重庆三峡医药高等专科学校,重庆404120

出　　处：《临床医学研究与实践》2022年第35期1-4,共4页Clinical Research and Practice

基　　金：重庆三峡医药高等专科学校自然科学类项目(No.2019XZYB09)。

摘　　要：目的基于网络药理学和分子对接探讨黄芪甲苷(AS-Ⅳ)、木香烃内酯(Cos)的抗乳腺癌(BC)机制。方法利用GeneCards、OMIM和TTD数据库检索BC相关靶点;利用Swiss TargetPrediction数据库和TargetNet在线平台筛选AS-Ⅳ、Cos相关靶点,将疾病与药物靶点进行重合以获得交集靶点。将交集靶点上传至STRING11.5在线数据平台构建蛋白质-蛋白质相互作用(PPI)网络,行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。利用AutoDock vina1.1.2进行分子对接。结果共获得17个AS-Ⅳ、Cos与BC的交集靶点,排名前4位的关键靶点为过氧化物酶体增殖物激活受体α(PPARα)、血管紧张素转换酶(ACE)、3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR)、B细胞淋巴瘤2相关蛋白A1(BCL2A1)。GO功能富集分析表明,AS-Ⅳ、Cos联合防治BC主要在老化、脂肪酸氧化调节、血压调节等方面起作用;KEGG通路富集分析表明,AS-Ⅳ、Cos联合防治BC可能涉及鞘脂类信号通路、腺苷酸活化蛋白激酶(AMPK)信号通路、血管平滑肌收缩等。分子对接显示,AS-Ⅳ、Cos与上述4个关键靶点的亲和力均较强。结论疾病与药物相关靶点具有重合性,AS-Ⅳ联合Cos可多靶点、多途径治疗BC。Objective To discuss the anti-breast cancer(BC)mechanism of astragalosideⅣ(AS-Ⅳ)and costunolide(Cos)based on network pharmacology and molecular docking.Methods BC related targets were retrieved from GeneCards,OMIM and TTD databases;AS-Ⅳand Cos related targets were screened from Swiss TargetPrediction database and TargetNet online platform,the disease and drug targets were overlaped to obtain intersection targets.The intersection targets were uploaded to the STRING11.5 online data platform to construct protein-protein interaction(PPI)network,and Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.AutoDock vina1.1.2 was used for molecular docking.Results A total of 17 intersection targets of AS-Ⅳ,Cos and BC were obtained,and the top four key targets were peroxisome proliferator activated receptorα(PPARα),angiotensin converting enzyme(ACE),3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR)and B cell lymphoma 2 related protein A1(BCL2A1).GO function enrichment analysis showed that the AS-Ⅳand Cos combined prevention and treatment of BC mainly played a role in aging,regulation of fatty acid oxidation and regulation of blood pressure;KEGG pathway enrichment analysis showed that AS-Ⅳand Cos combined prevention and treatment of BC might involve sphingolipid signaling pathway,adenosine monophosphate activated protein kinase(AMPK)signaling pathway,vascular smooth muscle contraction,etc.Molecular docking showed that AS-Ⅳand Cos had strong affinity with the above four key targets.Conclusion There is coincidence between disease and drug related targets,AS-Ⅳcombined with Cos can treat BC by multiple targets and pathways.

关 键 词：黄芪甲苷 木香烃内酯 乳腺癌 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]