化铁丸化学成分分析及其防治乳腺增生的潜在机制预测  

Chemical composition of Huatie compound and prediction of potential mechanism for prevention and treatment of hyperplasia of mammary glands

作　　者：曹琳 冉峥 侯强 邱作成[2] 杨建华[3] CAO Lin;RAN Zheng;HOU Qiang;QIU Zuocheng;YANG Jianhua(College of Pharmacy,Xinjiang Medical University,Urumqi Xinjiang 830054,China;Department of Internal Medicine,Fourth Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang 830054,China;Pharmaceutics Department of the First Affiliated Hospital of Xinjiang Medical University,Urumqi Xinjiang 830054,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830054 [2]新疆医科大学第四附属医院内科,新疆乌鲁木齐830054 [3]新疆医科大学第一附属医院药学部,新疆乌鲁木齐830054

出　　处：《中国药物警戒》2023年第10期1113-1120,共8页Chinese Journal of Pharmacovigilance

基　　金：国家自然科学基金资助项目(82160772)。

摘　　要：目的分析化铁丸处方中威灵仙和楮实子的化学成分并预测其防治乳腺增生的潜在作用机制,为后续揭示化铁丸药效物质基础及其防治乳腺增生潜在分子机制提供参考。方法利用UPLC-Orbitrap Exploris-MS技术,在正负离子模式下进行全扫描检测。通过中国知网、SciFinder、PubChem、TCMSP等数据库进行对比,分析化铁丸提取物(以80%甲醇为溶剂)的化学成分;采用网络药理学方法,通过类药性和口服生物利用度进行筛选,获得活性成分并利用SwissTargetPrediction数据库对化合物成分进行靶点预测,借助OMIM数据库获取乳腺增生相关靶点;采用String在线数据库构建蛋白质-蛋白质相互作用(PPI)网络图;通过DAVID数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路分析,并采用Cytoscape3.8.0软件构建“中药-活性成分-靶点-信号通路”网络图。结果从化铁丸中初步鉴定出101个化合物,包括22个萜类成分、22个黄酮类成分、14个苯丙素类成分、10个酚类成分、9个生物碱、9个氨基酸、4个酯类成分、4个脂肪酰类成分、4个脂肪酸类成分、2个山酮类成分、1个有机酸类成分。根据类药性(DL≥0.18)和口服生物利用度(OB≥30%)筛选出24个活性成分,通过OMIM数据库检索到2003个乳腺增生相关靶点基因,取交集得到化铁丸与乳腺增生交互靶点250个,PPI网络分析得出9个核心网络蛋白包括TNF、VEGFA、PI3KCA、PI3KR1、MAPK1、EGFR、AKT1、SRC、HSP90AA1。结论网络分析结果表明,化铁丸治疗乳腺增生与蛋白质磷酸化、信号转导、蛋白质自磷酸化等生物学过程有关。化铁丸中丰富的化学成分可能通过调节MAPK、Ras等信号通路发挥防治乳腺增生的作用。Objective To qualitatively analyze the chemical compositions of Huatie compound and predict the potential mechanism of Huatie compound in the prevention and treatment of breast hyperplasia,so as to lay a foundation for further revealing the pharmacodynamic material basis of Huatie compound and its potential molecular mechanism in the prevention and treatment of breast hyperplasia.Methods UPLC-Orbitrap Exploris-MS technology was used to perform full scan detection in positive and negative ion modes.The chemical compositions of Huatie compound extract(80%methanol as solvent)were analyzed by CNKI,SciFinder,PubChem,TCMSP and other databases.The network pharmacology method was used to screen the active ingredients through drug-likeness and oral bioavailability,and the SwissTargetPrediction database was used to predict the target of the compound components,and the OMIM database was used to obtain the target of breast hyperplasia.String online database was used to construct protein-protein interaction(PPI)network diagram.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed through DAVID database,and Cytoscape 3.8.0 software was used to construct a network diagram of‘Chinese medicine-active ingredient-target-signal pathway.Results 101 compounds were identified from Huatie compound,including 22 terpenoids,22 flavonoids,14 phenylpropanoids,10 phenols,9 alkaloids,9 amino acids,4 esters,4 fatty acids,4fatty acids,2 xanthones and 1 organic acid.Twenty-four active components were selected according to drug-like properties(DL≥0.18)and oral bioavailability(OB≥30%),and 2003 breast hyperplasia-related target genes were retrieved through the OMIM database,and 250 breast hyperplasia targets of Huatie compound were obtained by intersection.PPI network analysis showed that 9 core network proteins included TNF,VEGFA,PI3KCA,PI3KR1,MAPK1,EGFR,AKT1,SRC and HSP90AA1.Conclusion The results of network analysis showed that the treatment of hyperplasia of mammary glands wit

关 键 词：化铁丸 威灵仙 楮实子 乳腺增生 成分分析 液质联用 网络药理学 

分 类 号：R961[医药卫生—药理学] R977[医药卫生—药学]