基于网络药理学的半枝莲抗肿瘤活性成分及整合作用机制研究  

Active-component and integrative mechanism of Scutellaria barbata in treatment of cancer based on network pharmacology method

作　　者：杨沙 段灿灿 晏仁义 张建永[1] YANG Sha;DUAN Can-can;YAN Ren-yi;ZHANG Jian-yong(School of Pharmacy,Zunyi Medical University,Zunyi 563000,China;Key Laboratory Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi 563000,China;Tianjin Yibeiyuan Natural Products Technology Co.,Ltd.,Tianjin 300457,China)

机构地区：[1]遵义医学院药学院,贵州遵义563000 [2]遵义医学院基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563000 [3]天津益倍元天然产物技术有限公司,天津300457

出　　处：《中草药》2018年第15期3471-3482,共12页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金项目(81560736;81760746);贵州省教育厅科技拔尖人才支持项目(黔教合KY字[2017]078)

摘　　要：目的利用网络药理学方法探索半枝莲抗肿瘤的活性成分和分子作用机制。方法采用类药五原则筛选活性成分,经分子对接获得半枝莲活性成分的靶蛋白并于CTD数据库中获得靶点相对应的疾病,运用网络可视化软件,构建分子-靶点-疾病相互作用网络;同时进行蛋白质相互作用分析,通过生物学信息注释库(DAVID)对靶点进行生物代谢通路分析。结果半枝莲中有72个活性成分可与14个以上的肿瘤相关靶蛋白相互作用,半枝莲临泉生物碱D、barbatellarine E、半枝莲碱A等在内的二萜类成分是半枝莲抗肿瘤的主要活性成分。网络分析显示,半枝莲主要活性成分可作用于蛋白酪氨酸磷酸酶1B(PTP1B)、碳酸酐酶2(CA2)、周期蛋白依赖性激酶(CDK2)、视黄酸α受体(RXRA)等关键靶蛋白,参与调控VEGF信号通路、FcεRI信号通路以及Fox O信号通路。结论半枝莲可通过抗炎、抑制肿瘤血管生成等过程发挥多靶点、多通路的协同抗肿瘤作用。Objective To explore the active compounds and integrative mechanism of Scutellaria barbata in treatment of cancer by using network pharmacology. Methods The active components were screened by five rules of durability. The target proteins of S. barbata were obtained by molecular docking. The main diseases related to S. barbata were obtained by Comparative Toxicogenomics Database（CTD）. Then, the compound-target-disease interaction network was built using cytoscape 3.40. After protein-protein interaction analysis, Biological Information Annotation Databases（DAVID） was used to analyze the biological metabolic pathway of target proteins. Results A total of 72 compounds from S. barbata acted with more than 14 cancer-related targets, and diterpenoids including scutelinquninne D, barbatellarine E, and scutebarbatines A were the main active molecules of S. barbata. Network analysis showed that the active compounds of S. barbata can regulate VEGF signaling pathway, Fc epsilon RI signaling pathway, and Fox O signaling pathway through acting with the key targets protein, such as protein tyrosine phosphatase 1 B（PTP1 B）, carbonic anhydrase 2（CA2）, cyclic protein dependent kinases 2（CDK2）, retinoic acid α receptor（RXRA） and so on. Finally, S. barbata regulated the process of inflammation and tumor angiogenesis for its anticancer effect. Conclusion S.barbata can show the multi-target and multi-pathway synergistic antitumor activity through anti-inflammation and inhibiting tumor angiogenesis.

关 键 词：半枝莲 网络药理学 抗肿瘤 活性成分 作用机制 

分 类 号：R285.5[医药卫生—中药学]