基于网络药理学探讨二仙汤治疗骨质疏松症作用机制
Investigation of the mechanism of effect of Erxian decoction on osteoporosis based on network pharmacology
  
DOI:10.3969/j.issn.1006-7108.2020.05.016
中文关键词:  二仙汤  骨质疏松  网络药理学  信号通路
英文关键词:Erxian decoction  osteoporosis  network pharmacology  signaling pathways
基金项目:国家十三五重点研发计划(2018YFC1705600);广东省中医药局项目(20164008);广东省中医院治未病专项(YN2016ZWB07);广东省中医院中医药科技学术研究专项(YN2015QN08)
作者单位
史佩玉1 高帅1 綦向军1 莫嘉浩2 张唤唤1 朱俊霞1 陈国铭1 林樫1 方彩珊1 徐福平3* 1.广州中医药大学第一临床医学院广东 广州 510405 2.广州中医药大学第二临床医学院广东 广州 510405 3.广州中医药大学第二附属医院广东省中医院治未病中心广东 广州 510120 
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中文摘要:
      目的 基于网络药理学探讨二仙汤治疗骨质疏松症作用机制。方法 借助TCMSP和Uniprot数据库筛选二仙汤活性成分和作用靶标;通过TTD、Genecards、OMIM、DisGeNET在线数据库搜索骨质疏松症基因;运用Cytoscape3.7.0软件构建“二仙汤药物-活性成分-交集靶标基因”网络图;使用STRING数据库构建PPI网络并基于CytoHubba插件中的MCC算法筛选获得关键基因;运用g:Profiler对关键基因进行GO分析和KEGG通路富集分析,并使用Omicshare工具绘制高级气泡图,使用R软件绘制通路机制图。结果 二仙汤活性成分有104种,二仙汤作用靶标与骨质疏松症基因的交集靶标基因有145个,基于MCC算法得到关键基因50个。GO分析结果显示,生物途径主要包括信号转导、生物过程的阳性调节等;细胞组分包括胞内细胞器腔、核浆等;分子功能主要包括酶结合、信号受体结合等。KEGG富集通路结果显示关键基因主要富集在PI3K-Akt、MARK、NF-kB、TNF、Wnt、雌激素等信号通路。结论 二仙汤中的淫羊藿苷、槲皮素、山奈酚等活性成分可能通过PI3K-Akt、MARK、NF-kB、TNF、Wnt、雌激素等信号通路,作用于JUN、TNF-α、IL6、AR等多个关键基因,起到调节骨代谢,促进成骨细胞生成和抑制破骨细胞分化,治疗骨质疏松症的目的。
英文摘要:
      Objective To investigate the mechanism of Erxian decoction treatment for osteoporosis based on network pharmacology. Methods The active compounds and targets of Erxian decoction were obtained by using TCMSP and Uniprot database. Osteoporosis genes were obtained through TTD, Genecards, OMIM and DisGeNET online database. Cytoscape 3.7.0 software was used to construct the Erxian decoction drug-active ingredient-intersection target gene network map. STRING online database was used to build PPI Network and to screen key genes based on MCC Algorithms in Cyto Hubba Plug-in. G:Profiler was used for GO analysis and KEGG pathway enrichment analysis. Advanced bubble diagrams were plotted with Omicshare and pathway chart was plotted with R software. Results There were 104 active compounds of Erxian decoction and 145 intersection targets of osteoporosis. Fifty key genes were identified based on MCC algorithm. GO analysis results showed that biological pathways mainly included signal transduction, positive regulation of biological processes and cell components include intracellular organelles, and nuclear plasma, etc. Molecular functions mainly included enzymatic binding and signal receptor binding, etc. KEGG pathway enrichment showed that key genes were mainly concentrated in PI3K-Akt, MARK, NF-kB, TNF, Wnt, and estrogen signaling pathways. Conclusion The active ingredients such as icariin, quercetin, and kaempferol in Erxian decoction may be enriched in PI3K-Akt, MARK, NF-kB, TNF, Wnt, estrogen, and other signaling pathways through JUN, TNF-a, IL6, AR and other key genes to regulate bone metabolism, to promote osteoblast formation, to inhibit osteoclast differentiation, and to treat osteoporosis.
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