基于网络药理学探究苁蓉益肾颗粒调治骨质疏松的分子机制及初步验证  

Molecular mechanism study on the regulation of osteoporosis by Congrongyishen Granules based on network pharmacology and its preliminary validation

作　　者：孙冉 曾韬 杨彪[1] 周波[1] Sun Ran;Zeng Tao;Yang Biao;Zhou Bo(Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学再生医学与医用生物资源开发应用省部共建协同创新中心,南宁530021

出　　处：《广西医科大学学报》2023年第5期777-785,共9页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81860655);广西科技计划项目(No.桂科AD17195086)。

摘　　要：目的:通过网络药理学探究苁蓉益肾颗粒调治骨质疏松的有效靶点及信号通路,探讨其潜在的分子机制。方法:首先,通过体外细胞实验验证苁蓉益肾颗粒是否可以在体外抑制破骨细胞的分化。其次,基于TCMSP中医药数据库筛选苁蓉益肾颗粒的活性成分及其作用靶点,利用GeneCards数据库获得骨质疏松的相关靶点,并在UniProt数据库中对靶点信息进行规范。再次,取两者的交集得到苁蓉益肾颗粒治疗骨质疏松的靶基因。最后,利用STRING 11.0数据库对药物和疾病的靶基因进行蛋白相互作用(PPI)分析,构建网络图,并上传至Cytoscape 3.9.1软件制作PPI网络图,使用MCODE分析其潜在蛋白质功能模块;利用Metascape数据库对核心靶基因进行GO富集分析和KEGG通路分析。结果:细胞实验结果表明,苁蓉益肾颗粒可以在体外抑制破骨细胞的生成。苁蓉益肾颗粒有69种活性成分,对应靶点220个,骨质疏松相关疾病靶点有1 167个。其中,苁蓉益肾颗粒治疗骨质疏松的主要活性成分有槲皮素、β-谷甾醇、山奈酚、异鼠李素和芝麻素等,核心靶点为NCOA2、PTGS2、PTGS1、HSP90AB1和PIK3CG等。KEGG通路涉及癌症信号通路、AGE-RAGE信号通路、NF-κB信号通路以及VEGF信号通路等。结论:网络药理学揭示了苁蓉益肾颗粒的多成分、多靶点、多通路特性,为进一步研究苁蓉益肾颗粒的治疗骨质疏松的机制提供了基础。Objective:To explore the effective targets and signaling pathways of Congrongyishen Granules in the treatment of osteoporosis and investigate its potential molecular mechanism through network pharmacology.Methods:First,cellular assay was used to verify whether Congrongyishen Granules could inhibit osteoclast differentiation in vitro.Then,the TCMSP database was used to screen the active ingredients and targets of Congrongyishen Granules,and the GeneCards database was used to obtain the relevant targets for osteoporosis,with the target information normalized in the Uniprot database.After that,the intersection of the both was taken to obtain the intersection genes of Congrongyishen Granules for the treatment of osteoporosis.Finally,protein-protein interaction(PPI) analysis was performed using STRING 11.0 database for drug and disease target genes to construct network diagrams,which were uploaded to Cytoscape 3.9.1 software to produce PPI network diagrams and whose potential protein functional modules were analyzed using MCODE.GO enrichment analysis and KEGG pathway analysis were also performed on the core target genes using Metascape database.Results:The results of cellular assay showed that Congrongyishen Granules could inhibit osteoclastogenesis in vitro.There were 69 active ingredients of Congrongyishen Granules,corresponding to 220 targets,and there were 1,167 osteoporosis-related disease targets.Among them,the main active ingredients of Congrongyishen Granules for osteoporosis were quercetin,β-sitosterol,kaempferol,isorhamnetin and sesamin,etc.The core targets were NCOA2,PTGS2,PTGS1,HSP90AB1 and PIK3CG,etc.The KEGG pathway involved cancer signaling pathway,AGE-RAGE signaling pathway,NF-κB signaling pathway,VEGF signaling pathway,etc.Conclusion:The multi-component,multi-target,and multi-pathway features of Congrongyishen Granules are revealed by network pharmacology,providing a foundation for future study on the mechanism of Congrongyishen Granules in the treatment of osteoporosis.

关 键 词：苁蓉益肾颗粒 骨质疏松 网络药理学 

分 类 号：R285.5[医药卫生—中药学]