摘要
目的:利用网络药理学研究复方生地合剂治疗系统性红斑狼疮的关键靶标和潜在分子机制。方法:通过中国科学院化学数据库和文献搜索构建药材化合物成分数据库,以分子类药性DL、口服生物利用度OB、Lipinski规则和Veber规则筛选活性化合物,并以TCMSP和STITCH数据库预测活性成分靶点,GeneCards、TTD数据库获取系统性红斑狼疮相关靶点,两者相互映射得到复方生地合剂作用系统性红斑狼疮的交集靶点,STRING数据库构建蛋白质相互作用网络,DAVID数据库进行GO和KEGG分析,Cytoscape 3.7.1软件构建成分-靶点-通路网络,分析主要通路。结果:经筛选共获得复方生地合剂20个活性成分,对应285个靶点,46个为交集靶点,复方生地合剂的潜在活性成分为槲皮素、木犀草素等12个化合物,治疗关键靶点有肿瘤坏死因子、白介素6、白介素2等,主要作用于6条通路。结论:复方生地合剂可能通过细胞因子-细胞因子受体相互作用、丝裂原活化蛋白激酶信号通路等途径和基因表达、炎症反应、RNA聚合酶II启动子转录的正调控等生物过程发挥作用。
OBJECTIVE To study the key target and potential molecular mechanism of Fufang Shengdi Mixture in treating systemic lupus erythematosus(SLE)by network pharmacology.METHODS The chemical database of Chinese Academy of Sciences(CAS)and literature search were used to construct the compound composition database.The active compounds were screened by molecular drug-like DL,oral bioavailability OB,Lipinski rule and Veber rule.The targets of active ingredients were predicted by TCMSP and STITCH database.The related targets of systemic lupus erythematosus were obtained by GeneCards and TTD database,both of which were mapped to each other to obtain the intersection targets of Fufang Shengdi Mixture acting on systemic lupus erythematosus,the protein interaction network was constructed by STRING database,GO and KEGG analysis was performed by DAVID database,and the component-target-pathway network was constructed by Cytoscape 3.7.1 software to analyze the main pathways.RESULTS After screening,a total of 20 active components of Fufang Shengdi mixture were obtained,corresponding to 285 targets,46 of which are intersection targets.The potential active components of the Fufang shengdi mixture were quercetin,luteolin and 12 other compounds,and the key therapeutic targets were tumor necrosis factor,interleukin-6 and interleukin-2,which mainly acted on 6 pathways.CONCLUSION Fufang Shengdi mixture may play a role through the interaction of cytokine-cytokine receptor,the signaling pathway of mitogen-activated protein kinase and other biological processes such as gene expression,inflammatory response and positive regulation of RNA polymerase II promoter transcription.
作者
唐加龙
陈健
曹永兵
张立超
TANG Jia-long;CHEN Jian;CAO Yong-bing;ZHANG Li-chao(Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai TCM University,Shanghai 200071,China;Department of Pharmacy,Shanghai Traditional Chinese Medicine Hospital,Shanghai 200082,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第24期2500-2506,共7页
Chinese Journal of Hospital Pharmacy
基金
上海市科委科技创新行动计划(编号:18401932700)
关键词
网络药理学
复方生地合剂
系统性红斑狼疮
network pharmacology
Fufang Shengdi mixture
systemic lupus erythematosus
