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基于网络药理学预测左归丸治疗骨质疏松症作用机制

Mechanism of Zuogui Pill(左归丸) in the Treatment of Osteoporosis Based on the Network Pharmacology
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摘要 目的基于网络药理学预测左归丸有效成分治疗骨质疏松症的作用靶点与信号通路。方法通过TCMSP、TCMID、BATMAN-TCM等数据库搜索左归丸药物成分及其成分相关靶点;以“osteoporosis”为关键词在GeneCards、OMIM等数据库搜索骨质疏松症的疾病相关靶点;制作韦恩图,获取交集靶点;使用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GO、KEGG富集分析,并将富集结果可视化。结果左归丸活性成分78种,治疗骨质疏松症的核心活性成分有槲皮素、山柰酚、黄豆黄素、薯蓣皂苷配基、β-谷甾醇等,其作用的靶点分别是PTGS2、MMP9、JUN、AKT1、ICAM1;PTGS2、JUN、AKT1、ICAM1;PTGS2;PTGS2、AKT1;PTGS2、JUN,对左归丸治疗骨质疏松症的131个潜在作用靶点进行蛋白互作分析亦提示PTGS2、MMP9、JUN、AKT1、ICAM1是左归丸治疗骨质疏松症的关键靶点。关键靶点的GO和KEGG富集分析显示:GO富集分析功能条目413条,其中生物过程(BP)314条,细胞组分(CC)34条,分子功能(MF)65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73条,包括癌症信号通路、TNF信号通路、乙型肝炎信号通路、类风湿性关节炎信号通路、HIF-1信号通路等。结论左归丸治疗骨质疏松症主要是通过槲皮素、山柰酚、薯蓣皂苷配基、β-谷甾醇等活性成分作用于PTGS2、MMP9、JUN、AKT1、ICAM1等关键靶点基因从而调节多条生物学功能与信号通路,最终达到治疗骨质疏松症的作用。 Objective To predict the target and signal pathway of Zuogui Pill(左归丸)in the treatment of osteoporosis based on network pharmacology.Methods The drug components and their related targets of Zuogui Pill were searched by TCMSP,TCMID,BATMAN-TCM databases,and the disease related targets of osteoporosis were searched in GeneCards and OMIM databases with the keywords“osteoporosis”;The common target of Zuogui Pill and osteoporosis were obtained by making Venny diagrams,and String database and Cytoscape softwwere were used to constructs the protein interaction network of drug-disease common target and drug-component-disease-target network.Finally,GO and KEGG enrichment analysis of common target was carried out through David database,and the enrichment results were visualized.Results There were 78 active ingredients in Zuogui Pill.The core active ingredients in treating osteoporosis were quercetin,kaempferol,glycitein,diosgenin,beta-sitosterol.The action targets of active ingredients were PTGS2,MMP9,JUN,AKT1,ICAM1;PTGS2,JUN,AKT1,ICAM1;PTGS2;PTGS2,AKT1;PTGS2,JUN,respectively.There were 131 potential targets of Zuogui Pill in treating osteoporosis protein interaction analysis also suggested that PTGS2,MMP9,JUN,AKT1 and ICAM1 were the key targets of Zuogui Pill in the treatment of osteoporosis.There were 413 functional items were analyzed by GO enrichment analysis,including 314 biological processes(BP),34 cell components(CC),65 molecular function(MF),including cell response to lipopolysaccharide,steroid hormone receptor activity,etc;There were 73 KEGG signaling pathways,including cancer signaling pathway,TNF signaling pathway,hepatitis B signaling pathway,rheumatoid arthritis signaling pathway,HIF-1 signaling pathway,etc.Conclusion Zuogui Pill in the treatment of osteoporosis mainly through quercetin,kaempferol,diosgenin,beta-sitosterol act on PTGS2,MMP9,JUN,AKT1,ICAM1,so as to regulate multiple biological functions and signal pathways,and finally achieve the therapeutic effect.
作者 李伟 赵子义 穆晓红 陈黎明 李春根 LI Wei;ZHAO Ziyi;MU Xiaohong;CHEN Liming;LI Chungen(Beijing University of Traditional Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100700,China;The Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100029,China;Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University,Beijing 100010,China)
出处 《辽宁中医药大学学报》 CAS 2022年第8期70-75,共6页 Journal of Liaoning University of Traditional Chinese Medicine
基金 国家自然科学基金面上项目(81874467) 北京中医药大学青年教师项目(2019-JYB-JS-160) 北京中医药大学东直门医院科技创新专项(DZMKJCX-2020-047)。
关键词 骨质疏松症 左归丸 网络药理学 信号通路 osteoporosis Zuogui Pill(左归丸) network pharmacology signal pathways
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