文献类型：期刊文献

中文题名：基于网络药理学和分子对接的红芪活性成分抗阿霉素心肌毒性的分子机制研究

英文题名：Study on the mechanism of active composition of Radix Hedysari against doxorubicin induced myocardial toxicity based on network pharmacology and molecular docking

作者：杨秀娟[1,2,4];田一虹[1,2];杨志军[1,2];梁婷婷[1];李硕[1,2];李越峰[1,2,3]

第一作者：杨秀娟

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃省中医药研究中心,甘肃兰州730000;[3]敦煌医学与转化教育部重点实验室,甘肃兰州730000;[4]西北中藏药协同创新中心,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2021

卷号：31

期号：3

起止页码：209

中文期刊名：中国药物化学杂志

外文期刊名：Chinese Journal of Medicinal Chemistry

收录：CSTPCD;;CSCD:【CSCD_E2021_2022】；

基金：国家自然科学基金项目(81960713);甘肃省教育厅高等学校科研项目(2017A-056);敦煌医学与转化教育部重点实验室开放基金项目(DHYX18-11);甘肃省中医药管理局科研课题基金资金项目(GZK-2017-7);甘肃省高校重大疾病分子医学与中医药防治研究重点实验室开放基金项目(FZYX17-18-4);甘肃省中医药研究中心开放基金项目(zyzx-2020-22);甘肃省青年科技基金项目(20JR10RA331)。

语种：中文

中文关键词：红芪;网络药理学;分子对接;阿霉素致心肌毒性;分子机制

外文关键词：Radix Hedysari;network pharmacology;molecular docking;myocardial toxicity of doxorubicin;molecular mechanism

摘要：目的基于网络药理学和分子对接研究红芪活性成分抗阿霉素心肌毒性的作用机制。方法通过系统药理学平台(traditional chinese medicine systems pharmacology,TCMSP)、瑞士靶点预测数据库(swiss target prediction)检索红芪化学成分及对应靶点。以毒性基因数据库(comparative toxicogenomics database,CTD)、基因卡片数据库(GeneCards)分别得到阿霉素毒性靶点、心肌损伤靶点。阿霉素致心肌毒性靶点与药物靶点进行映射,得到红芪抗阿霉素心肌毒性的靶点,通过STRING 11.0在线平台进行蛋白互作(protein-protein interaction,PPI),运用注释、可视化和集成发现的数据库(database for annotation,visualization and integrated discovery,DAVID)进行基因本体(gene ontology,GO)功能富集和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集。最后,通过Autodock软件对红芪的关键活性成分与作用靶点进行分子对接。结果收集红芪活性成分14个、阿霉素致心肌毒性靶点2203个、红芪抗阿霉素心肌毒性潜在靶点37个。PPI结果显示表皮生长因子受体(epidermal growth factor receptor,EGFR)、前列腺素内过氧化物合酶2(prostaglandin peroxidase 2,PTGS2)、基质金属蛋白酶2(matrix metalloproteinase 2,MMP2)、单胺氧化酶B(monoamine oxidase B,MAOB)等可能是红芪抗阿霉素致心肌毒性的关键靶点。GO功能富集主要涉及单一生物代谢过程、脂质代谢过程、氧化还原酶活性、细胞外区域等。KEGG信号通路主要包括色氨酸代谢、酪氨酸代谢、花生四烯酸代谢等。分子对接结果显示毛蕊异黄酮、槲皮素、芒柄花素、食脂素与PTGS2、EGFR、MMP2、MAOB有效好的结合活性。结论红芪中活性化合物毛蕊异黄酮、槲皮素、芒柄花素、食脂素等可能作用于PTGS2、EGFR、MMP2、MAOB等靶点调节花生四烯酸代谢、氧化还原酶活性、ErbB等多条信号通路,发挥抗阿霉素心肌毒性的作用。
The study mainly conducted the mechanism of Radix Hedysari against doxorubicin induced myocardial toxicity based on network pharmacology and molecular docking.The chemical components and corresponding targets of Radix Hedysari were retrieved through traditional chinese medicine systems pharmacology(TCM SP) and swiss target prediction.The comparative toxicogenomics database(CTD) and GeneCards database were used to search doxorubicin induced toxicity targets and myocardial injury-related targets respectively.Using Cytoscape 3.4.0 software to construct a myocardial toxicity netw ork of Radix Hedysari against doxorubicin.37 Potential targets that Radix Hedysari against doxorubicin-induced myocardial toxicity were obtained after mapping.The above targets were input into STRING 11.0 for Protein-Protein Interaction Networks analysis(PPI),which showed EGFR,PTGS2,MMP2,MAOB,etc.may be the key targets of Radix Hedysari against doxorubicin-induced myocardial toxicity.Gene ontology (GO)biological function enrichment mainly involved single biological metabolic process,lipid metabolic process,oxidoreductase activity,extracellular region and so on.The ryoto encyclopedia of genes and genomes(KEGG) pathway mainly included tryptophan metabolism,tyrosine metabolism,arachidonic acid metabolism and so on.Molecular docking results showed that calycosin,quercetin,formononetin,[(2S)-7-hydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one](DFV) had good binding with PTGS2,EGFR,MMP2,MAOB.The calycosin,quercetin,formononetin,DFV,which were active compounds in Radix Hedysari,can regulate arachidonic acid metabolism,xidoreductase activity and ErbB signal pathways such as PTGS2,EGFR,MMP2 and MAOB,so as to reveal the effect of Radix Hedysari against doxorubicin induced myocardial toxicity.