基于网络药理学和分子对接挖掘黑骨藤治疗强直性脊柱炎的作用机制

Exploring the Action Mechanism of Periploca Forrestii in Treating Ankylosing Spondylitis Based on Network Pharmacology and Molecular Docking

目的:运用网络药理学技术研究黑骨藤治疗强直性脊柱炎的作用机制。方法:通过检索文献和TCMSP数据库获取黑骨藤的活性成分信息。疾病靶点基因由DISGENET数据库和GeneCards数据库获得,通过瑞士目标预测数据库预测药物成分靶点,借助cytoscape软件构建“中药-化合物-靶点”网络,使用STRING在线平台下载靶点相互作用数据,构建PPI蛋白相互作用网络,挖掘核心靶点;运用DAVID平台对所预测核心靶点网络中的蛋白进行GO功能富集分析、KEGG通路富集分析。最后将筛选出的主要活性成分与核心靶点在pymol、autotool等软件下完成分子对接。结果:筛选出黑骨藤12个有效成分及422个药物靶点,与强直性脊柱炎交集靶点71个,其主要成分有异丙基二烯酚、汉黄芩素、山奈酚等,核心靶点是STAT3、MAPK1、MAPK14、JAK2、JAK1等。GO功能和KEGG通路分析获得主要通路:参与生长激素信号通路JAK-STAT级联反应、JAK-STAT级联、STAT蛋白的酪氨酸磷酸化、Th17细胞分化、Th1和Th2细胞分化等。分子对接显示,成分与靶点都可有效结合,汉黄芩素与JAK1结构最优。结论:从网络药理学角度预测了黑骨藤对强直性脊柱炎的治疗作用,主要以汉黄芩素、山奈酚等有效成分,作用于JAK1、JAK2等靶点,通过JAK/STAT、MAPK等信号通路实现,为后续研究奠定了的基础。

Objective:To study the action mechanism of Periploca forrestii in the treatment of ankylosing spondylitis using network pharmacology technology.Methods:The active ingredient information of Periploca forrestii was retrieved through literature search and TCMSP database.The disease target genes were obtained from the DISGENET database and GeneCards database,and drug component targets were predicted using the Swiss target prediction database.A“Chinese medicine-compound-target”network was constructed using cytoscape software,and target interaction data was downloaded using the STRING online platform.A PPI protein interaction network was constructed to explore core targets;the DAVID platform was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on proteins in the predicted core target network.Finally,the selected main active ingredients and core targets were subjected to molecular docking using software such as Pymol and Autotool.Results:Twelve effective ingredients and 422 drug targets were screened from Periploca forrestii,and 71 targets intersected with ankylosing spondylitis.The main components of Periploca forrestii included isopropyldienol,baicalin,and kaempferol,while the core targets were STAT3,MAPK1,MAPK14,JAK2 and JAK1.GO function and KEGG pathway analysis revealed the main pathways involved in the growth hormone signaling pathway JAK-STAT cascade,JAK-STAT cascade,tyrosine phosphorylation of STAT protein,Th17 cell differentiation,Th1 and Th2 cell differentiation.Molecular docking showed that both components and targets could effectively bind,and the structure of baicalin and JAK1 was optimal.Conclusion:From the perspective of network pharmacology,the therapeutic effect of Periploca forrestii on ankylosing spondylitis was predicted,mainly using effective ingredients such as baicalin and kaempferol,which acted on targets such as JAK1 and JAK2 through signaling pathways such as JAK/STAT and MAPK,laying a certain foundation for subsequent research.