摘要
目的:运用网络药理学研究杜仲-牛膝有效成分治疗骨质疏松症(Osteoporosis,OP)的分子作用机制。方法:运用相关数据库,分别筛选出骨质疏松症的疾病靶标及杜仲-牛膝的中药活性成分与相应的靶标,通过两组预测靶点相互映射,获得中药-疾病共同靶标并构建中药-疾病-靶标调控网络。然后通过构建共同靶标的蛋白互作网络,筛选核心靶点基因。最后将核心靶点进行基因本体生物学过程(Gene Ontology-biological Process,GO)功能富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)功能富集分析。结果:在中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)中检索杜仲-牛膝,通过药物的吸收、分布、代谢和排泄(ADME)参数筛选和PubMed数据库验证,最终获得杜仲-牛膝活性成分34种,利用靶基因预测技术获得靶基因193个。通过疾病数据库获取与OP相关的靶基因336个。将两组基因相互映射,获得杜仲-牛膝作用于OP的关键靶基因14个,核心靶点9个。基因富集结果显示,杜仲-牛膝干预OP主要通过癌症信号通路、缺氧诱导因子1(HIF-1)信号通路、Toll样受体信号通路、胰岛素抵抗信号通路、腺苷酸活化蛋白激酶(AMPK)信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K-Akt)信号通路等。结论:杜仲-牛膝干预OP具有多组分、多靶点、协同作用的特点,通过以PI3K-Akt、AMPK、HIF-1等为主的众多信号通路下的关键靶基因对骨代谢产生双向调控作用,促进成骨作用;同时激活大量间接靶点,通过调节人体内分泌、改变离子通道状态、影响骨周围组织代谢等途径对骨代谢产生综合影响。
Objective:The molecular mechanism of the effective components of Duzhong-Niuxi(杜仲-牛膝)herb-partners on osteoporosis was studied based on network pharmacology.Methods:Using related databases,the disease targets of osteoporosis,and the TCM active ingredients of Duzhong-Niuxi herb-partners and the corresponding targets were screened out.Through the mutual mapping of the two sets of prediction targets,the common target of TCM medicines-diseases was obtained and the TCM medicinesdiseases-targets regulatory network was constructed.Then,the core target genes were screened by constructing a common target protein interaction network.Finally,the GO function enrichment analysis and the KECG function enrichment analysis of the core targets were performed.Results:Duzhong-Niuxi herb-partners were retrieved in TCMSP,34 active ingredients of Duzhong-Niuxi herb-partners were finally obtained according to ADME screening and PubMed verification;and 193 target genes were obtained according to target gene prediction technology.336 target genes related to OP were obtained in diseases databases.14 key target genes and 9 core targets of Duzhong-Niuxi herb-partners on osteoporosis were obtained after mapping the two sets of genes to each other.The gene enrichment results showed that Duzhong-Niuxi herb-partners mainly interfered with osteoporosis through cancer signaling pathway,HIF-1 signaling pathway,Toll-like receptor signaling pathway,insulin resistance signaling pathway,AMPK signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:The intervention of Duzhong-Niuxi herb-partners on OP was characterized by multi-component,multi-target and synergistic effects.Bone production was promoted by the two-way regulation of key target genes on bone metabolism under many signal pathways such as PI3K-AKT,AMPK,HIF-1,etc..At the same time,a large number of indirect targets were activated,which has a comprehensive effect on bone metabolism by regulating human endocrine,changing the state of ion channels,and affecting the metabolism of bone
出处
《中医临床研究》
2020年第35期1-6,共6页
Clinical Journal Of Chinese Medicine
关键词
网络药理学
杜仲-牛膝
骨质疏松症
信号通路
Network pharmacology
Duzhong-Niuxi herb-partners
Osteoporosis
A signaling pathway
