文献类型：期刊文献

中文题名：基于中医药整合药理学平台、GEO数据库芯片及分子对接探讨大黄抗肝癌的作用机制

英文题名：Mechanism of anti-hepatoma of Rhei Radix et Rhizoma based on integrative pharmacology platform,GEO database chip and molecular docking

作者：王玉[1];杨雪[4];靳晓杰[1];杨飞霞[1];王玉霞[1];王菲[1];樊秦[1];张建[1];武晓玉[1];夏鹏飞[1,2,3];赵磊[1,2,3]

第一作者：王玉

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]甘肃中医药大学甘肃省高校中藏药化学与质量研究省级重点实验室,甘肃兰州730000;[3]甘肃省道地药材质量标准化技术研究与推广工程实验室,甘肃兰州730000;[4]北京中医药大学药学院,北京102488

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2020

卷号：51

期号：20

起止页码：5207

中文期刊名：中草药

外文期刊名：Chinese Traditional and Herbal Drugs

收录：CSTPCD;;Scopus;北大核心:【北大核心2017】；CSCD:【CSCD2019_2020】；

基金：国家自然科学基金资助项目(81660577);青海省藏药药理学和安全性评价研究重点实验室开发课题(2018-ZY-05);甘肃省道地药材质量标准化技术研究与推广工程实验室开放基金项目(ddyc-2016-04);甘肃省中医药管理局科研项目(G2K-2014-77)。

语种：中文

中文关键词：整合药理学平台;GEO数据库;分子对接;大黄;肝癌;成分-靶点-通路;大黄酸;大黄素;大黄酚-8-O-β-D-葡萄糖苷;大黄酚-1-O-β-D-葡萄糖苷;丹叶大黄素

外文关键词：integrative pharmacology platform;GEO database;molecular docking;Rhei Radix et Rhizoma;hepatoma;component-target-pathway;rhein;emodin;chrysophanol-8-O-β-D-glucoside;chrysophanol-1-O-β-D-glucoside;rhapontigenin

摘要：目的采用GEO数据库、整合药理学平台v2.0和分子对接技术探讨大黄抗肝癌的活性成分及其分子机制。方法利用中医药整合药理学平台(TCMIP)筛选中药大黄的活性成分,借助TCMIP及Swisstarget在线数据库预测作用靶点;从GEO数据库下载肝癌基因芯片数据库,利用GEO2R分析肝癌组织与正常肝组织之间的差异表达基因。基于大黄潜在靶点与肝癌靶点的匹配结果筛选大黄抗肝癌的关键靶点,并对关键靶点进行基因本体论(GO)功能、基因组百科全书(KEGG)通路富集分析。通过构建蛋白互作网络(PPI)、成分-靶点网络及中药-成分-靶点-通路网络,分析并筛选大黄抗肝癌的主要成分和核心靶点。进一步采用Schrodinger-Maestro软件对核心靶点与主要活性成分进行分子对接,以虚拟验证其结合能力并分析其结合模式。结果筛选得到大黄抗肝癌活性成分20个,作用靶点86个,涉及CDK1、AKR1C3、PTGS2、AR、CCNB1等。GO功能富集主要集中在细胞周期、有丝分裂、氧化还原过程、药物反应、类固醇代谢过程等。KEGG通路富集主要涉及细胞周期、细胞衰老、补体系统、花生四烯酸代谢、胆汁代谢等,且这些代谢通路与细胞凋亡、转移、炎症和免疫相关。分子对接结果显示92.2%的活性成分与10个核心靶蛋白均具有较好的结合力,且结合形式多以氢键、疏水键、π-π键和阳离子-π键为主。结论大黄中的大黄酸、大黄素、大黄酚-8-O-β-D-吡喃葡萄糖苷、大黄酚-1-O-β-D-葡萄糖苷、丹叶大黄素等活性成分能够作用于CDK1、CCNB1、CYP2C9、MMP9、PTGS2等多个靶点,通过调节与细胞凋亡、转移、炎症、免疫相关的信号通路进而发挥抗肝癌作用。
Objective To investigate the anti-hepatoma active components of Rhei Radix et Rhizoma and their molecular mechanisms through GEO database,integrative pharmacology platform and molecular docking technology.Method The active ingredients of Rhei Radix et Rhizoma were screened by TCMIP and the corresponding targets of these components were predicted through TCMIP and Swisstarget databases.The hepatoma gene chip database was downloaded from GEO databases,and the differentially expressed genes between hepatocellular carcinoma(HCC)and normal liver tissue were analyzed by GEO2R.Based on the matching results of potential targets of Rhei Radix et Rhizoma and the targets of hepatoma,the key targets of Rhei Radix et Rhizoma against hepatoma were screened,and GO function enrichment and KEGG pathway enrichment analysis of the key targets were performed.Main components and core targets of Rhei Radix et Rhizoma against hepatoma were analyzed and screened by constructing PPI network,component-target network and traditional Chinese medicine-component-target-pathway network.Furthermore,the molecular docking between the core targets and the main active components was performed by Schrodinger-Maestro software to virtually verify their binding ability and analyze their binding mode.Result A total of 20 anti-hepatoma active components of Rhei Radix et Rhizoma were collected and related 86 targets were obtained,including CDK1,AKR1C3,PTGS2,AR and CCNB1,etc.The results of GO functional enrichment mainly focused on the cell cycle,G2/M transition of mitotic cell cycle,oxidation-reduction process,drug reactions and steroid metabolism processes,etc.The results of KEGG pathway enrichment mainly involved cell cycle,cell senescence,complement system,arachidonic acid metabolism and bile metabolism,and these metabolic pathways were related to cell apoptosis,metastasis,inflammation and immunity.The results of molecular docking showed that 92.2%of the active components had good binding ability with the 10 core proteins,and the main combination forms mainly were hydrogen bonds,hydrophobic bonds,π-πbonds and cation-π.Conclusion The active components of Rhei Radix et Rhizoma including rhein,emodin,chrysophanol-8-O-β-D-glucopyranoside,chrysophanol-1-O-β-D-glucoside and rhapontigenin can act on multiple targets such as CDK1,CCNB1,CYP2C9,MMP9 and PTGS2,by regulating signaling pathways related to cell apoptosis,metastasis,inflammation and immunity to play an anti-hepatoma effect.