基于网络药理学的元胡止痛方治疗骨关节炎的作用机制研究

Mechanism of Yuanhuzhitong decotion for osteoarthritis based on network pharmacology

目的:从网络药理学角度探讨元胡止痛方治疗骨关节炎的作用机制。方法:从TCMSP数据库中筛选出元胡止痛方的有效活性成分,然后提取活性成分的作用靶点,使用Cytoscape构建“药物-成分-靶点”网络图。通过OMIM、GeneCards、DisGeNET数据库获得骨关节炎疾病基因。随后将药物靶点与疾病靶点进行映射,通过STRING在线数据库获得关键靶点蛋白与蛋白相互作用(PPI)关系,通过Clue GO插件对关键靶点进行GO功能富集分析以及KEGG信号通路富集分析。结果:通过OB≥30%、DL≥0.18的阈值筛选获得生物碱类、香豆素类、挥发油类及甾体类等共71个活性成分和99个唯一靶点,通过疾病数据库获得骨关节炎靶点1546个;通过靶点映射共获得共同作用靶点45个,其中核心靶点有IL6、VEGFA、CASP3、CCND1、ESR1等。GO富集分析发现元胡止痛方治疗OA的生物过程主要富集在细胞迁移、分化、核苷酸代谢和合成、RNA聚合酶Ⅱ对pri-miRNA转录的调控、细胞凋亡等方面。KEGG分析显示元胡止痛方可能作用于HIF-1信号通路,TNF信号通路、NF-κB信号通路等通路。表明元胡止痛方中主要活性成分可通过“多成分-多靶点-多通路”来发挥治疗骨性关节炎的作用。结论:本研究从网络药理学角度分析了元胡止痛方的主要活性成分、关键靶点及信号通路,为进一步探讨其作用机制奠定了基础。

Objective:To study the mechanism of Yuanhuzhitong decoction for the treatment of osteoarthritis from the perspective of network pharmacology.Methods:The active ingredients of Yuanhuzhitong decoction were screened out from the TCMSP database,and then the targets of the active ingredients were extracted.The drug-ingredient-target network was constructed using Cytoscape.The genes of osteoarthritis were obtained by OMIM,GeneCards and DisGeNET databases.Drug targets and disease targets were mapped together,and the relationship of the key target protein-protein interaction(PPI)was obtained through the online STRING database.Key targets were analyzed by Clue GO plug-in for GO functional enrichment and KEGG signaling pathway enrichment.Results:A total of 71 active ingredients and 99 unique targets of alkaloids,coumarins,volatile oils,steroids,etc were obtained through the threshold of OB≥30%and DL≥0.18.45 common targets were obtained through Venn diagram,among which the core targets were IL6,VEGFA,CASP3,CCND1,ESR1,etc.GO enrichment analysis revealed that the biological processes of Yuanhu Zhitong decoction for OA were mainly concentrated in cell migration,differentiation,nucleotide metabolism and synthesis,regulation of pri-miRNA transcription by RNA polymeraseⅡ,and apoptosis.KEGG analysis showed that Yuanhuzhitong decoction may act on HIF-1 signal pathway,TNF signal pathway,NF-κB signal pathway and other pathways.The results showed that the main active ingredients in Yuanhuzhitong decoction could play an important role for the treatment of osteoarthritis through"multi-component,multi-target and multi-pathway".Conclusion:This study analyzed the main active ingredients,key targets,signaling pathways and mechanism of Yuanhuzhitong decoction from the perspective of network pharmacology,laying a foundation for further exploration of its mechanism.