基于网络药理学探讨仙灵骨葆胶囊治疗骨质疏松症的作用机制  

Analysis of pharmacological mechanism of XianlingGubao capsule in treating osteoporosis based on network pharmacology

作　　者：綦向军 陈国铭[1] 史佩玉 张兆萍 方彩珊 郑深建 邢万里 黎健敏 周润吉 徐福平 QI Xiangjun;CHEN Guoming;SHI Peiyu;ZHANG Zhaoping;FANG Caishan;ZHENG Shenjian;XING Wanli;LI Jianmin;ZHOU Runji;XU Fuping(The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510405;Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Preventive Center of Guangdong Hospital of Traditional Chinese Medicine, Guangzhou 510120, China)

机构地区：[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附属医院,广东省中医院治未病中心,广东广州510120

出　　处：《中国骨质疏松杂志》2020年第5期710-718,730,共10页Chinese Journal of Osteoporosis

基　　金：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)。

摘　　要：目的运用网络药理学分析方法进行仙灵骨葆治疗骨质疏松症(osteoporosis,OP)的药理机制分析。方法借助中药系统药理学数据库和分析平台以及中药综合数据库获取仙灵骨葆活性成分以及相关靶标,运用Cytoscape 3.7.1软件绘制“活性成分-靶标”网络图,以“osteoporosis”为关键词从GeneCards:The Human Gene Database获取OP相关基因,运用STRING数据分析平台进行PPI(protein-protein interaction)网络分析,运用DAVID数据分析平台进行基因本体(gene ontology,GO)生物过程富集以及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析,并运用Cytoscape 3.7.1软件绘制“通路-靶标”网络图。结果共获取仙灵骨葆相关活性成分115种,核心活性成分有槲皮素、山奈酚、木犀草素、淫羊藿苷元、丹参酮IIA等。活性成分所涉及的靶标共有301个,核心靶标有PTGS2、PTGS1、ESR1等。PPI网络显示了111种核心蛋白之间的互作关系,主要与调节细胞周期有关。GO富集生物过程经筛选后共获得46项,所得生物过程亦与细胞周期有关,正调控NF-kappaB转录活性因子的过程是OP发生的机制之一,与现有研究符合。KEGG通路富集共获得37项,提示仙灵骨葆治疗OP作用集中于PI3K-Akt、TNF、MAPK、Estrogen等信号通路。结论仙灵骨葆核心活性成分中,黄酮类化合物主要通过调节OPG/RANK/RANKL,抑制破骨细胞,促进成骨细胞分化;淫羊藿苷元可增强成骨细胞活性。核心靶标PTGS2可限制M-CSF以及RANKL的表达,进而影响成骨/破骨细胞分化;雌激素受体与绝经后骨质疏松密切相关。核心通路如PI3K-Akt信号通路可增加骨量、促进成骨细胞分化;TNF信号通路、MAPK信号通路等均与成骨细胞分化有关;雌激素信号通路以及GnRh信号通路为仙灵骨葆干预绝经后骨质疏松提供依据。因此仙灵骨葆干预OP机制是通过多种途径、多种靶标、多种信号通路同时�Objective To analyze the pharmacological mechanism of the treatment of osteoporosis(OP)with XianlingGubao Capsule(XGC)based on network pharmacology.Methods The active components and related targets of XGC were obtained by means of the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Traditional Chinese Medicine Integrated Database(TCMID),and Cytoscape(ver.3.7.1)was adopted for constructing the active component-target network.With OP as the key word,OP-related genes were obtained from Gene Cards:The Human Gene Database.Thereafter,Gene Ontology(GO)bioprocess enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using DAVID data analysis platform.STRING data analysis platform and Cytoscape were respectively applied for PPI network analysis and the construction of passage-target network.Results A total of 115 active components related to XGC were obtained,of which the core active components contain quercetin,kaempferol,luteolin,icariin,tanshinone IIA,etc.280 targets are involved with the active components,whose core targets consist of PTGS2,PTGS1,ESR1,etc.The PPI network analysis demonstrated an interaction of 111 kinds of core protein,indicating a major relation with cell cycle regulation.Likewise,46 biological processes obtained through the screening of GO enrichment are associated with cell cycle regulation as well.The process of positively regulating NF-κB transcriptional activator is one of the mechanisms of OP,which is consistent with the findings of other studies.Moreover,the KEGG pathway enrichment screened out 37 pathways in total,suggesting that the effects of XGC on OP focus on PI3K-Akt,TNF,MAPK,estrogen and other signaling pathways.Conclusion As for the core active components of XGC,flavonoids inhibit osteoclast and promote osteoblast differentiation mainly by regulating OPG/RANK/RANKL,while icaritin can improve the activity of osteoblast.In terms of the core targets,PTGS2 can restrict the expressions of M-CSF

关 键 词：骨质疏松症 仙灵骨葆 网络药理学 基因本体 通路富集 蛋白质-蛋白质相互作用 

分 类 号：R285.6[医药卫生—中药学]