基于网络药理学预测独活寄生汤治疗强直性脊柱炎作用机制

Prediction of the Mechanism of Duhuo Jisheng Decoction(独活寄生汤)in the Treatment of Ankylosing Spondylitis Based on Network Pharmacology

目的基于网络药理学预测独活寄生汤治疗强直性脊柱炎的作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、中药分子机制综合数据库(TCMID)、中药分子机制生物信息学分析工具(BATMANTCM)等数据库搜索独活寄生汤中各药物成分及其相关靶点,以Ankylosing spondylitis为关键词在DrugBank、GeneCards、OMIM、TTD等数据库搜索强直性脊柱炎的疾病相关靶点,通过制作韦恩图,获取药物-疾病交集靶点,利用String数据库、Cytoscape 3.6.1软件构建药物-疾病交集靶点蛋白互作网络、药物-成分-疾病-靶点网络,最后通过DAVID数据库对药物-疾病交集靶点进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析,并将富集结果可视化。结果通过TCMSP、TCMID、BATMAN-TCM三个数据库共获得独活寄生汤药物化学成分264个,包括槲皮素、山柰酚、柚皮素、汉黄芩素、黄芩素等;有效成分与强直性脊柱炎共同作用靶点129个,包括肿瘤坏死因子(TNF)、白细胞介素6(IL6)、脂多糖受体(CD14)、前列腺素内过氧化物合酶1(PTGS1)等;GO富集分析功能条目547条,其中生物过程(BP)435条,细胞组分(CC)40条,分子功能(MF)72条,包括细胞对脂多糖的反应、类固醇激素受体活性等;KEGG信号通路共101条,主要包括核因子κB(NF-kB)信号通路、核苷酸结合寡聚域(NOD)样受体信号通路、低氧诱导因子-1(HIF-1)信号通路、催乳素信号通路等。结论独活寄生汤治疗强直性脊柱炎主要是通过槲皮素、山柰酚、柚皮素、汉黄芩素、黄芩素等活性成分作用于信号转导和转录激活因子3(STAT3)、白细胞介素1β(IL1B)、血管内皮生长因子(VEGFA)、白细胞介素10(IL10)等关键靶点基因从而调节多条生物学功能与信号通路,最终达到治疗强直性脊柱炎作用。

Objective To predict the mechanism of Duhuo Jisheng Decoction(独活寄生汤)in the treatment of ankylosing spondylitis based on network pharmacology.Methods TCMSP,TCMID,BATMAN-TCM databases were used to search the drug components and related targets of Duhuo Jisheng Decoction;Objective to search the disease-related targets of ankylosing spondylitis in DrugBank,GeneCards,OMIM,TTD databases with the key words of“ankylosing spondylitis”.The common target of Duhuo Jisheng Decoction and ankylosing spondylitis were obtained by making Venny diagrams,and String database and Cytoscape software were used to constructs the protein interaction network of drug-disease common target and drug-component-disease-target network.Finally,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of common target is carried out through David database,and the enrichment results are visualized.Results Through TCMSP,TCMID,BATMAN-TCM databases,264 chemical components of Duhuo Jisheng Decoction were obtained,including quercetin,kaempferol,naringenin,wogonin,baicalein,etc;129 common targets of active components and ankylosing spondylitis,including tumor necrosis factor(TNF),interleukin-6(IL6),lipopolysaccharide receptor(CD14),prostaglandin endoperoxide synthase 1(PTGS1),etc;547 functional items were analyzed by GO enrichment analysis,including 435 biological processes(BP)and 40 cell components(CC),72 molecular function(MF),including cell response to lipopolysaccharide,steroid hormone receptor activity,etc;There were 101 KEGG signaling pathways,including nuclear factor KB(NF-KB)signaling pathway,NOD like receptor signaling pathway,hypoxia inducible factor-1(HIF-1)signaling pathway,prolactin signaling pathway,etc.Conclusion Duhuo Jisheng Decoction in the treatment of ankylosing spondylitis mainly through quercetin,kaempferol,naringenin,wogonin,baicalein act on Signal transducer and activator of transcription 3(STAT3),interleukin 1β(IL1 B),vascular endothelial growth factor(VEGFA),interleukin 10(IL10),so as to regulate multiple biological functions and signal pathways,and finally achieve the therapeutic effect.