| 摘要: |
| 目的：基于网络药理学及分子对接技术研究桃仁-红花治疗膝骨关节炎（KOA）的作用机制。方法：采用TCMSP及Uniprot数据库收集整合桃仁、红花的活性成分及其药理作用靶点，在GeneCards数据库检索KOA的靶点基因，通过Venny获取疾病-药物交互靶点，借助STRING 数据库及Cytoscape软件构建蛋白互作网络图并上传Metascape数据库进行GO功能和 KEGG通路富集分析，最后运用 AutoDock和Pymol将核心有效成分与相应的关键靶点进行分子对接预测。结果：1）桃仁-红花有效活性成分45个，主要成分为槲皮素、山柰酚、木犀草素等；2）KOA与药物的共同靶点120个，丝氨酸/苏氨酸蛋白激酶1（AKT1）、转录因子AP-1（JUN）、肿瘤坏死因子（TNF）、细胞肿瘤抗p53（TP53）、转录因子p65（RELA）、丝裂原激活的蛋白激酶1（MAPK1）、白细胞介素6（IL-6）、热休克蛋白（HSP90AA1）、血管内皮生长因子A （VEGFA）、丝裂原激活的蛋白激酶8（MAPK8）等为关键靶点；3）分子对接结果显示山柰酚可靶向结合AKT1、TNF；4）GO功能富集分析得出桃仁-红花治疗KOA主要涉及细胞增殖、生长因子的反应、细胞应激反应的调节、细胞死亡的正调控等生物合成过程；5）KEGG通路富集分析显示白细胞介素17（IL-17）、雌激素信号通路为桃仁-红花干预KOA的主要信号通路。结论：桃仁-红花中的槲皮素、山柰酚、木犀草素等有效成分通过AKT1、JUN、TNF、TP53、RELA、MAPK1、IL-6、HSP90AA1、VEGFA、MAPK8等关键靶点与IL-17和雌激素信号通路等主要通路发挥抗炎、调控细胞增殖、凋亡及应激反应的方式治疗KOA。 |
| 关键词: 膝骨关节炎 桃仁-红花 网络药理学 分子对接 |
| DOI： |
|
|
| Mechanism of action of peach seed-Carthamus tinctorius in treatment of knee osteoarthritis based on network pharmacology and molecular docking |
| WU Jie,WU Ruizhe,GE Shuwei |
| (Hunan University of Chinese Medicine，Changsha 410208，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of peach seed-Carthamus tinctorius in the treatment of knee osteoarthritis （KOA） based on network pharmacology and molecular docking.Methods：TCMSP and Uniprot databases were used to collect the active components and pharmacological action targets of peach seed and Carthamus tinctorius，and GeneCards database was used to search for the target genes of KOA.Venny diagram was used to obtain disease-drug interaction targets，and STRING database and Cytoscape software were used to construct a protein-protein interaction network and upload it into Metascape database for GO and KEGG pathway enrichment analyses.Finally AutoDock and Pymol were used to predict the molecular docking of core effective components and corresponding key targets.Results：1）A total of 45 effective components were obtained for peach seed-Carthamus tinctorius，mainly quercetin，kaempferol，and luteolin.2）There were 120 common targets of KOA and the drug combination，and the key targets included serine/threonine protein kinase 1 （AKT1），transcription factor AP-1 （JUN），tumor necrosis factor （TNF），tumor protein p53 （TP53），transcription factor p65 （RELA），mitogen-activated protein kinase1 （MAPK1），interleukin-6 （IL-6），heat shock protein （HSP90AA1），vascular endothelial growth factor A （VEGFA），andmitogen-activated protein kinase 8 （MAPK8）.3）Molecular docking showed the targeted binding of kaempferol to AKT1 and TNF.4）GO enrichment analysis showed that the treatment of KOA with peach seed-Carthamus tinctorius involved the biological processes such as cell proliferation，growth factor response，regulation of cell stress response，and positive regulation of cell death.5）KEGG pathway enrichment analysis showed that the interleukin-17 （IL-17） signaling pathway and the estrogen signaling pathway were the main signaling pathways involved in the intervention of KOA by peach seed-Carthamus tinctorius.Conclusion：The effective components of peach seed-Carthamus tinctorius such as quercetin，kaempferol，and luteolin have a therapeutic effect on KOA by exerting an anti-inflammatory effect and regulating cell proliferation，apoptosis，and stress response via the key targets including AKT1，JUN，TNF，TP53，RELA，MAPK1，IL-6，HSP90AA1，VEGFA，and MAPK8 and the signaling pathways including IL-17 and estrogen. |
| Key words: knee osteoarthritis peach seed-Carthamus tinctorius network pharmacology molecular docking |
