[关键词]
[摘要]
目的 采用网络药理学方法和分子对接技术,探讨巴戟天治疗类风湿性关节炎(rheumatoid arthritis,RA)的作用机制。方法 通过TCMSP、GeneCards、OMIM、TTD以及String数据库获得巴戟天活性成分、作用靶点以及RA相关疾病靶点,采用Cytoscape 3.7.1软件绘制“化学成分-靶点-RA”网络图,采用String和DAVID数据库进行蛋白质-蛋白质相互作用(protein-protein interaction,PPI)、基因本体(gene ontology,GO)功能及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析,使用Chemdraw、PyMOL、AutoDock Tools软件以及RCSB PDB数据库对活性成分与关键靶点进行分子对接。结果 共筛选出11个巴戟天活性成分和37个关键靶点,GO功能和KEGG通路富集分析显示巴戟天可能通过信号转导、RNA聚合酶II启动子的转录起始、蛋白质结合、三磷酸腺苷(adenosine triphosphate,ATP)结合等生物学过程,作用于哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、Janus激酶1(Janus kinase 1,JAK1)、JAK2、半胱氨酸蛋白酶-1(Caspase-1)、髓样细胞白血病蛋白1(myeloid cell leukemia 1,MCL1)等关键靶点的表达,进一步调控磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)-蛋白激酶B(protein kinase B,Akt)信号通路、癌症信号通路、HTLV-1感染等信号通路,从而治疗RA。分子对接结果显示,巴戟天中活性成分与关键靶点间存在分子结合位点。结论 巴戟天能够通过多成分、多靶点、多通路、多机制治疗RA。
[Key word]
[Abstract]
Objective To explore the mechanism of Bajitian (Morindae Officinalis Radix) in treatment of rheumatoid arthritis (RA) by using network pharmacology methods and molecular docking. Methods Active ingredient and action targets of Morindae Officinalis Radix, and RA-related disease targets were obtained through TCMSP, GeneCards, OMIM, TTD and String databases; Cytoscape 3.7.1 software was used to draw "active ingredient-target-RA" network diagram; String and DAVID database were used for protein-protein interaction (PPI), gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Molecular docking of active ingredient and key targets were performed by Chemdraw, PyMOL, AutoDock Tools software and RCSB PDB database. Results A total of 11 active ingredients and 37 key targets of Morindae Officinalis Radix were screened out. GO function and KEGG pathway enrichment analysis showed that Morindae Officinalis Radix may treat RA through biological processes such as signal transduction, transcription initiation of RNA polymerase II promoter, protein binding, and adenosine triphosphate (ATP) binding, acting on key targets such as mammalian target of rapamycin (mTOR), Janus kinase 1 (JAK1), JAK2, Caspase-1, myeloid cell leukemia protein 1 (MCL1), regulating signaling pathways such as phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) signaling pathway, cancer signaling pathway and HTLV-1 infection. Molecular docking results showed that there were molecular binding sites between active components of Morindae Officinalis Radix and key targets. Conclusion Morindae Officinalis Radix can treat RA through multiple components, multiple targets, multiple pathways and multiple mechanisms.
[中图分类号]
R285.5
[基金项目]