摘要
目的运用网络药理学和反向分子对接技术探讨西红花抗肿瘤的作用机制。方法通过检索文献和从中药系统药理学数据库(TCMSP)获取西红花的主要化学成分,利用PharmMapper服务器预测西红花活性成分的潜在靶点,通过UniProt数据库将西红花潜在靶点转换为对应的靶标基因,与GeneCards、OMIM和TTD数据库获得的肿瘤相关靶点进行映射分析,得到西红花抗肿瘤的潜在作用靶点。采用Cytoscape软件构建西红花“活性成分-靶点-疾病”相互作用网络,通过String数据库进行蛋白-蛋白相互作用分析,并利用Metascape平台进行GO功能和KEGG通路富集分析。使用AutoDock、Pymol软件对活性成分与关键靶点进行分子对接验证。结果共筛选出西红花中槲皮素、山柰酚、异鼠李素、苦番红花素和西红花苷Ⅰ等9个活性成分,可能作用于AKT1、CCND1、MMP9、EGFR、TP53等37个关键靶点,涉及P53信号通路及TNF信号通路等。分子对接显示可通过氢键、疏水作用等产生稳定结合。结论初步探讨了西红花抗肿瘤的主要活性成分、关键靶点及通路,提示可通过诱导细胞凋亡等方式发挥抗肿瘤作用,为后续实验验证提供参考依据。
Objective To explore the anti-tumor mechanism of saffron(Crocus sativus L.)by network pharmacology and reverse molecular docking techniques.Methods The main chemical components of saffron were obtained by searching published literature and TCMSP database.The potential targets of these components were predicted using PharmMapper server.The corresponding target genes were identified from UniProt database.The underlying anti-tumor targets of saffron were obtained by mapping the disease genes of cancer or tumor with GeneCards,OMIM and TTD databases.Cytoscape software was used to construct the action target network of saffron active components.The protein-protein interaction analysis was performed by String database,and the GO function and KEGG pathway enrichment analysis were performed by Metascape platform.Finally,molecular docking was performed to evaluate the binding of main components with their potential targets.Results A total of 9 active ingredients in saffron including quercetin,kaempferol,isorhamnetin,picrocrocin and crocin I,were identified,which might act on 37 key targets including AKT1,CCND1,MMP9,EGFR,TP53,involved in P53,TNF and other signaling pathways.Molecular docking indicated modest binding potency through hydrogen bonding,and hydrophobic interactions.Conclusion The anti-tumor effect of saffron was evaluated via the network of components-targets-pathways,which might provide a foundation for further research.
作者
孟祥庆
李丽华
王宏瑞
贾丹
贾敏
MENG Xiangqing;LI Lihua;WANG Hongrui;JIA Dan;JIA Min(School of Pharmacy,Naval Medical University,Shanghai 200433,China)
出处
《药学实践与服务》
CAS
2023年第3期160-167,196,共9页
Journal of Pharmaceutical Practice and Service
基金
基于可再生能源的极端环境绿色空间生命支撑系统研究(BX221C010)
西红花种球植物工厂化生产关键技术研究(2021CNKC-04-01)。
关键词
西红花
网络药理学
分子对接
抗肿瘤
saffron
network pharmacology
molecular docking
anti-tumor mechanism
