摘要
目的:鉴定楤木醇提物中非皂苷类化学成分并探究其治疗乳腺癌的作用机制。方法:采用超高效液相-四级杆-静电场轨道阱高分辨质谱(UPLC-Q-Exactive Orbitrap MS)采集数据,结合数据库检索和相关文献比对,鉴定楤木非皂苷类化学成分;利用SwissTargetPrediction平台预测化学成分作用靶点,GeneCards、OMIM、TTD数据库获得疾病相关靶点,取成分与疾病交集靶点做蛋白相互作用(protein protein interaction,PPI)分析、GO生物功能和KEGG信号途径富集分析,采用SYBYL2.1.1软件对非皂苷类成分与核心靶点进行分子对接验证,最后应用分子动力学模拟对化合物和靶点相互作用关系进行验证。结果:楤木醇提物中共鉴定出29个化合物;获得成分与疾病交集靶点412个,交集靶点GO功能富集3 258个条目、KEGG通路富集192条通路;分子对接结果显示成分与靶点蛋白结合活性良好;分子动力学模拟提示异绿原酸C和AKT1间的相互作用稳定。结论:楤木可能通过作用于TP53等靶点,调控PI3K-AKT等信号通路,以“多成分-多靶点-多途径”方式发挥治疗乳腺癌的作用。
OBJECTIVE To identify the chemical constituents of non-saponins in the ethanol extract of Aralia chinensis L.and to explore its mechanism of action in the treatment of breast cancer.METHODS The data were collected by ultra-high per⁃formance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Q-Exactive Orbitrap MS),and the non-saponin chemical constituents of Aralia chinensis L.were identified by database searching and litera⁃ture review.The SwissTargetPrediction platform was used to predict the targets of chemical components.GeneCards,Online Mendelian Inheritance in Man(OMIM)and Therapeutic Target Database(TTD)were searched to obtain disease-related tar⁃gets.Protein protein interaction(PPI)analysis,Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signal pathway enrichment analysis were performed on the intersection targets of components and diseases.SYBYL 2.1.1 software was used to verify the molecular docking of non-saponin components and core targets.Finally,molecular dynamics simulation was used to verify the interaction between compounds and target genes.RESULTS A total of 29 compounds were identified in the ethanol extract of Aralia chinensis L.A total of 412 intersection targets of components and dis⁃ease targets of breast cancer were obtained.Totally,3258 biological items were enriched in GO function,and 192 enriched signal⁃ing pathways were analyzed by KEGG pathway.Molecular docking results showed that the components had good binding activity with the target proteins.Molecular dynamics simulation suggested that the interaction between isochlorogenic acid C and AKT1 was stable.CONCLUSION Aralia chinensis L.may exert its therapeutic effects on breast cancer through a multi-component,multi-target,multi-pathway mechanism by acting on targets like TP53 and regulating signaling pathways like the PI3K-AKT.
作者
薛娟
刘龙江
田燕
李磊
舒永佳
柴慧芳
XUE Juan;LIU Longjiang;TIAN Yan;LI Lei;SHU Yongjia;CHAI Huifang(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guizhou Guiyang 550025,China)
出处
《中国医院药学杂志》
北大核心
2025年第13期1475-1479,共5页
Chinese Journal of Hospital Pharmacy
基金
贵州省科技计划项目(编号:黔科合基础[2020]1Y389)。
关键词
楤木
UPLC-MS
网络药理学
乳腺癌
分子对接
分子动力学模拟
Aralia chinensis L.
UPLC-MS
network pharmacology
breast cancer
molecular docking
molecular dynamics simulation
