基于网络药理学预测金匮肾气丸治疗骨质疏松症的作用机制

Mechanism of Jinkui Shenqi Pill inTreatment of Osteoporosis Based on Network Pharmacology

目的:基于网络药理学预测金匮肾气丸治疗骨质疏松症的作用机制。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(BATMAN-TCM)等数据库检索金匮肾气丸药物成分及成分相关靶点;以“Osteoporosis”为关键词在人类基因数据库(GeneCards)、在线人类孟德尔遗传数据库(OMIM)、DrugBank等数据库检索骨质疏松症疾病相关靶点;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及药物-成分-疾病-靶点网络;通过DAVID数据库对药物-疾病交集靶点进行基因本体(GO)、京都基因和基因组百科全书(KEGG)富集分析,并将富集结果可视化。结果:共获得金匮肾气丸药物成分118个,包括槲皮素、山柰酚、大黄素等;有效成分相关靶点202个,疾病相关靶点1856个,药物-疾病交集靶点87个,包括前列腺素内过氧化物合酶2(PTGS2)、转录因子(JUN)、胞间黏附分子1(ICAM1)等;GO富集分析功能条目376条,其中生物过程(BP)290条,细胞组分(CC)28条,分子功能(MF)58条,包括RNA聚合酶Ⅱ启动子的转录正调控、类固醇激素受体活性等;KEGG信号通路共90条,包括类风湿性关节炎信号通路、破骨细胞分化信号通路、催乳激素信号通路等。结论:金匮肾气丸通过槲皮素、山柰酚、大黄素、薯蓣皂苷元、β-谷甾醇等有效成分作用于PTGS2、JUN、ICAM1、白细胞介素-1β(IL-1β)、基质金属蛋白酶9(MMP9)等关键靶点通过抗氧化、抑制炎症反应、促进成骨细胞增殖分化、抑制破骨细胞骨吸收等作用机制达到治疗OP的作用。

To predict the mechanism of Jinkui Shenqi Pill in the treatment of osteoporosis based on network pharmacology.Methods TCMSP,TCMID,BATMAN-TCM databases were used to retrieve the drug components and related targets of Jinkui Shenqi pill;the related targets of osteoporosis were searched in GeneCards,OMIM,DrugBank databases with the key word of“osteoporosis”;the common target of the drug-disease were obtained by generating Venny diagrams;string database and Cytoscape 3.6.1 software were used to construct the drug-disease common target protein interaction network and drug-component-disease-target network;finally,GO and KEGG enrichment analysis of common target were carried out through David database,and the enrichment results were visualized.Result A total of 118 chemical components from Jinkui Shenqi pill were obtained,including quercetin,kaempferol,emodin,etc.;there were 202 active component related targets,1856 disease-related targets and 87 drug-disease common targets,including PTGS2,JUN,ICAM1,etc.;there were 376 functional items analyzed by GO enrichment analysis,namely 290 biological processes(BP),28 cellular components(CC)and 58 molecular functions(MF),including the positive regulation of transcription from RNA polymeraseⅡpromoter and steroid hormone receptor activity;there were 90 KEGG signaling pathways,mainly including rheumatoid arthritis signaling pathway,osteoclast differentiation signaling pathway,prolactin signaling pathway,etc.Conclusion Jinkui Shenqi Pill functions mainly through quercetin,kaempferol,emodin,diosgenin and beta-sitosterol on key target genes of PTGS2,JUN,ICAM1,IL1B and MMP9 through the mechanism of anti-oxidation,inhibition of inflammatory reaction,promotion of osteoblast proliferation and differentiation,inhibition of osteoclast bone absorption,and finally achieve the therapeutic effect of treat OP.