基于网络药理学研究寒湿痹颗粒治疗强直性脊柱炎的机制

Mechanism of Hanshi Bi granules in the treatment of ankylosing spondylitis based on network pharmacology

背景:寒湿痹颗粒已被临床中用于治疗强直性脊柱炎,但其药理作用机制不明确。目的:基于网络药理学的方法,对寒湿痹颗粒的主要化学成分进行筛选,并收集其化合物对应的靶点,并构建化合物-靶点网络,对其治疗强直性脊柱炎的药理作用机制进行系统阐述。方法:寒湿痹颗粒化合物及与药物靶点的收集主要基于TCMSP数据库及文献报道,强直性脊柱炎疾病靶点来源于DRUGBANK、GeneCards、Home-OMIM-NCBI、PALM-IST数据库。所获得药物基因和疾病基因经过Uniprot数据库校正后使用Draw Venn Diagrams分析工具获得交集基因。结合STRING数据库与Cytoscape3.6.1对交集基因进行PPI分析。通过使用Cytoscape3.6.1插件ClueGO对交集基因进行GO富集分析及KEGG通路富集分析。结果与结论:①从TCMSP获得69个活性成分,142个药物靶点,利用DRUGBANK、GeneCards、Home-OMIM-NCBI、PALM-IST数据库获得595个强直性脊柱炎疾病靶点;②使用Draw Venn Diagrams工具分析获得交集基因39个,通过PPI分析,肿瘤坏死因子、白细胞介素6、前列腺素内过氧化物合酶2在PPI网络中连接度较高;③通过GO富集分析发现,其主要涉及活性氧代谢调节、脂肪酸代谢、急性炎症反应、神经递质的生物过程、花生四烯酸的代谢等生物功能;④通过KEGG通路富集分析发现,其主要涉及AGE-RAGE信号通路、流体剪切应力和动脉粥样硬化、白细胞介素17信号通路、核因子κB信号通路、肿瘤坏死因子信号通路、Toll样受体信号通路等;⑤研究初步预测寒湿痹颗粒治疗强直性脊柱炎的药理作用机制,为老药新用及实验研究提供新思路。

BACKGROUND:Hanshi Bi granule has been used to treat ankylosing spondylitis in the clinic,but the pharmacological mechanism B is still unclear.OBJECTIVE:To screen the compound and drug targets of Hanshi Bi granules based on network pharmacology.and construct a compound-target network to systematically investigate the pharmacological mechanism for treating ankylosing spondylitis.METHODS:The compounds and drug targets of Hanshi Bi granules were collected from TCMSP database.Ankylosing spondylitis targets were from DRUGBANK,GeneCards,Home-OMIM-NCBI,and PALM-IST databases.The obtained drug targets and disease targets were corrected by Uniprot database and common genes were obtained using Draw Venn Diagrams analysis tool.PPI analysis was performed on the common gene in combination with the STRING database and Cytoscape 3.6.1.GO enrichment analysis and KEGG pathway enrichment analysis were performed on the common gene by using Cytoscape 3.6.1 plugin ClueGO.RESULTS AND CONCLUSION:(1)Totally 69 active ingredients and 142 drug targets were obtained from TCMSP,and 595 ankylosing spondylitis targets were obtained using DRUGBANK,GeneCards,Home-OMIM-NCBI,and PALM-IST databases.(2)Using the Draw Venn Diagrams tool to analyze all targets,39 common genes were obtained.Through PPI analysis,tumor necrosis factor,interleukin-6 and prostaglandin-in-peroxidase 2 were highly connected in the PPI network.(3)Through GO enrichment analysis,it mainly involved biological functions such as regulation of reactive oxygen metabolism,fatty acid metabolism,acute inflammatory reaction,neurotransmitter biosynthetic process,and metabolism of arachidonic acid.(4)Through KEGG pathway enrichment analysis,it mainly involved in AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis,interleukin-17 signaling pathway,nuclear factor-κB signaling pathway,tumor necrosis factor signaling pathway,and Toll-like receptor signaling pathway.(5)This study preliminarily predicts the pharmacological mechanism underlying the treatment of ankylosing spondylitis with Hanshi Bi granules,and provides new ideas for secondary development of old drugs and experimental research.