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基于系统药理学的骨碎补治疗骨质疏松的通路及靶标探讨
赵金龙1,2, 曾令烽2,3, 赵第1,2, 潘建科2,3, 韩燕鸿1,2, 梁桂洪2,3, 李嘉晖1,2, 刘军2,3
1.广州中医药大学第二临床医学院, 广州 510405;2.广东省中医药科学院骨与关节退变及损伤研究团队, 广州 510120;3.广州中医药大学第二附属医院, 广东省中医院, 广州 510120
摘要:
[目的]通过系统药理学相关生物信息学分析方法探讨中药材骨碎补治疗骨质疏松的的生物学通路及靶标。[方法]通过中药系统药理学分析平台(TCMSP)数据库提取骨碎补的活性成分和有关的靶标蛋白。通过运用软件Cytoscape 3.5.1构筑骨碎补有效成分与靶标关系网络进行拓扑学分析。使用STRING数据库进行蛋白之间相互作用(PPI)网络的构筑与分析。借助David数据库进行KEGG通路功能富集分析。[结果]表明骨碎补的核心化合物有柚皮苷、圣草酚、山奈酚等,重要的靶标有前列腺素G/H合成酶2(Prostaglandin G/H synthase 2)、Heat shock protein HSP 90、Caspase-3等,骨碎补发挥生物学效应作用于骨质疏松症的关键蛋白主要有JUN、TP53、MAPK1、白介素-6(IL-6)、雌激素受体1(ESR1)等。KEGG结果表明骨碎补主要作用于TNF signaling pathway、T cell receptor signaling pathway、HIF-1 signaling pathway、PI3K-Akt signaling pathway、Estrogen signaling pathway等相关信号通路。[结论]骨碎补主要通过多种途径,多种信号通路作用于多种靶点发挥抗骨质疏松的生物学效用。
关键词:  骨碎补  骨质疏松  系统药理学  通路  靶标  机制
DOI:10.11656/j.issn.1672-1519.2019.11.24
分类号:R681
基金项目:广东省财政厅项目([2014]157,[2018]8);广东省中医院中医药科学技术研究专项项目(YK2013B2N19,YN2015MS15);广东省医学科学技术研究基金项目(B2019091);广东省普通高校重点科研平台和科研项目(2018KQNCX041)。
Pathways and targets of Gusuibu in the treatment of osteoporosis based on systematic pharmacology
ZHAO Jinlong1,2, ZENG Lingfeng2,3, ZHAO Di1,2, PAN Jianke2,3, HAN Yanhong1,2, LIANG Guihong2,3, LI Jiahui1,2, LIU Jun2,3
1.Second Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Guagnzhou 510405, China;2.Guangdong Academy of Traditional Chinese Medicine, Research Team on Bone and Joint Degeneration and Injury, Guangzhou 510120, China;3.Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510120, China
Abstract:
[Objective] To explore the biological pathway and target of gusuibu in the treatment of osteoporosis by systematic pharmacology-related bioinformatics analysis.[Methods] The active constituents and target proteins of Gusuibu were extracted from TCMSP database. By using Cytoscape 3.5.1 to construct the relationship network between effective components and target of gusuibu for topological analysis. STRING10.5 database was used to construct and analyze protein-protein interaction (PPI) network. KEGG pathway function enrichment analysis was carried out with the help of David database.[Results] Naringin,eriodic tyol and kaempferol were the core compounds of Gusuibu. Prostaglandin G/H synthase 2,Heat shock protein HSP 90 and Caspase-3 were the important targets. JUN,TP53,MAPK1,IL-6,ESR1 were the key proteins in the effective components of gusuibu. KEGG results showed that osteoporosis mainly acted on TNF signaling pathway,T cell receptor signaling pathway,HIF-1 signaling pathway,PI3K-Akt signaling pathway,estrogen signaling pathway and other related signaling pathways.[Conclusion] Gusuibu has the biological effect of anti-osteoporosis through a variety of pathways and signaling pathways acting on a variety of targets.
Key words:  Gusuibu  osteoporosis  systemic pharmacology  pathway  target  mechanism
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