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作 者:闫浩 刘小毛 左振宇[1] 刘靖丽[1] 宋逍[1] YAN Hao;LIU Xiaomao;ZUO Zhenyu;LIU Jingli;SONG Xiao(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,Shaanxi,China)
出 处:《中华中医药学刊》2020年第11期245-250,I0054,I0055,共8页Chinese Archives of Traditional Chinese Medicine
基 金:陕西省高校科协青年人才托举计划(20170406);陕西省自然科学基础研究计划(2019JQ-874);陕西省教育厅专项科研计划(19JK0232);陕西中医药大学自然科学培育基金(2016PY19)。
摘 要:目的采用网络药理学方法探讨山茱萸的物质基础及抗糖尿病作用机制。方法采用类药性评估筛选山茱萸活性成分,进而查找化合物作用靶点;查找糖尿病相关靶点;将有效成分靶点和疾病靶点进行韦恩映射,借助Cytoscape构建药物、成分、靶点、疾病网络图;应用string PPI构建蛋白互作网络;利用Bioconductor对核心靶点进行GO和KEGG富集。结果从山茱萸中筛选得到20个候选活性成分,筛选出50个蛋白靶点;通过OMIM、Genecards疾病数据库筛选出与糖尿病相关的靶点8690个,韦恩映射得到46个交集基因,富集得到71条基因功能和56条通路具有抗糖尿病作用,PPI核心网络中度值排名前20的关键节点有12个富集在前10位信号通路中,依次为CASP3, JUN, MAOA, MAOB, SLC6A4, CHRM, ADR(ADRA1D, ADRA1A, ADRA1B, ADRB2, ADRA2C, ADRA2A)。结论通过网络药理学验证了山茱萸多成分、多靶点、多途径调节的作用特点,预测了山茱萸在抗糖尿病中的主要作用机制,为后续实验研究提供物质基础和理论依据。Objective In this study, network pharmacology was adopted to explore the substance basis and anti-diabetes mechanism of Shanzhuyu(Fructus Corniin). Methods Drug-likeness(DL) evaluation was used to search the chemical ingredients of Shanzhuyu(Fructus Corniin) and screened diabetes targets through OMIM and Genecards databases. Mapping Wayne was carried out between effectively active compound targets and disease targets. The network of drugs, components, targets and diseases was established by Cytoscape. A protein interaction network was constructed by using string PPI. GO function and KEGG pathway enrichment were performed on the core targets by Bioconductor. Results For Shanzhuyu(Fructus Corniin), 20 candidate active components were obtained and 50 corresponding protein targets were screened. A total of 8690 targets related to diabetes were obtained by OMIM and Genecards disease database. Then by mapping Wayne, 71 items and 56 pathways were obtained by enrichment analysis against diabetes. A total of 12 key nodes from the top 20 nodes from PPI network were enriched in the top 10 signaling pathway,respectively CASP3, JUN, MAOA, MAOB, SLC6 A4, CHRM, ADR(ADRA1 D, ADRA1 A, ADRA1 B, ADRB2, ADRA2 C, ADRA2 A). Conclusion The characteristics of multi-component, multi-target and multi-channel regulation of Shanzhuyu(Fructus Corniin) were verified by network pharmacology. The main anti-diabetes mechanism of Shanzhuyu(Fructus Corniin) was predicted, which provided substance basis and theoretical basis for subsequent experimental research.
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