基于网络药理学的三味檀香散治疗冠心病的机制初探  

A preliminary study on mechanisms of Sanwei Tanxiang powder based on network pharmacology

作　　者：孙雨辉 陆景坤 王健[3] 王跃武[4] 张谦[4] 范蕾 那生桑 贾宇臣 SUN Yu-hui;LU Jing-kun;WANG Jian;WANG Yue-wu;ZHANG Qian;FAN Lei;NA Sheng-sang;JIA Yu-chen(a. College of Pharmacy, b. Basic Medical College, c. Preclinical Drug Safety Evaluation Center, d. Mongolian Medicine Research Institute, Inner Mongolia Medical University, Hohhot INNER MONGOLIA 010059, China;Key Laboratory of Structure- Based Drug Design ＆ Discovery, Ministry of Education, Shenyang Pharmaceutical Universtity , Shenyang LIA ONING 110016, China)

机构地区：[1]内蒙古医科大学药学院,内蒙古呼和浩特010059 [2]内蒙古医科大学基础医学院,内蒙古呼和浩特010059 [3]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016 [4]内蒙古医科大学临床前药物安全评价中心,内蒙古呼和浩特010059 [5]内蒙古医科大学蒙医药研究院,内蒙古呼和浩特010059

出　　处：《中国新药与临床杂志》2018年第5期272-289,共18页Chinese Journal of New Drugs and Clinical Remedies

基　　金：内蒙古自然科学基金(2017MS0845);内蒙古自治区科技创新引导奖励资金项目(02039003)

摘　　要：目的探讨蒙药三味檀香散治疗冠心病的分子作用机制和潜在活性成分。方法通过文献挖掘、多个中药材成分数据库检索收集整理三味檀香散中化学成分,并经口服生物利用度(OB)和类药性(DL)分析筛选。利用Pharm Mapper、SWISS、Superpred在线平台预测化合物潜在靶点,OMIM数据库收集冠心病的相关靶标。利用STRING做蛋白互作分析,通过DAVID在线工具对关键靶标做通路富集。应用Cytoscape软件建立该方剂的"方剂-靶点-冠心病药物网络模型"和"方剂-化合物-靶点-通路网络模型",并对网络模型进行拓扑学分析。采用Schrodinger分子对接技术对网络模型分析部分结果进行验证。结果网络药理学结果表明,蒙药方剂三味檀香散与冠心病发病机制相关的生物学途径主要有应激反应、血管新生、免疫炎症反应、细胞损伤、凋亡及坏死、内分泌调节、细胞分裂增殖、动脉粥样硬化、动脉斑块的不稳定性。TP53、ADORA1、AKT1、MDM2等靶点可能是三味檀香散治疗冠心病的关键靶点。结论三味檀香散可能通过其主要成分与多个靶点蛋白作用,调控冠心病发展过程中的应激反应、血管生成、免疫炎症反应、能量代谢、内分泌调节等多条生物通路治疗冠心病。AIM To explore the molecular mechanisms and potential active ingredients of the MongolianSanwei Tanxiang powder on coronary heart disease（CHD）.METHODS The chemical composition in Sanwei Tanxiang powder was collected by literature mining and Chinese herbal medicine composition database retrieval,and analyzed by oral bioavailability（OB） and drug-likeness（DL） screening.The potential targets of the compound were predicted by online platform of Pharm Mapper,SWISS and Superpred.The related targets of CHD were collected by OMIM database.Protein interaction was analyzed by STRING.The pathway of key target was predicted by the DAVID online tool.The formula of ＂drug prescriptions-targets-CHD network model＂ and＂prescriptions-compound-targets-pathway network model＂ were established by Cytoscape software,and topology analysis of network model was carried out.The results of the analysis of network model were verified by Schrodinger molecular docking technique.RESULTS The results of network pharmacology showed that the biological pathways related to in the pathogenesis of CHD caused by Sanwei Tanxiang powder may be involved in stress response,angiogenesis,immune inflammatory response,cell damage,apoptosis and necrosis,endocrine regulation,cell division and proliferation,atherosclerosis and arterial plaque instability.Cellular tumor antigen p53,adenosine receptor A1,RAC-alpha serine/threonine-protein kinase,E3 ubiquitin-protein ligase mdm2,etc.were likely to be the key target of Sanxiang Tanxiang powder for CHD.CONCLUSION Sanxiang Tanxiang powder may regulate multiple biological pathways in the development of CHD through the main composition and multiple target protein function,such as stress response,angiogenesis,immune inflammatory response,energy metabolism,endocrine regulation,etc.

关 键 词：蒙药 冠心病 药理作用分子作用机制 拓扑学 三味檀香散 网络药理学 

分 类 号：R972[医药卫生—药品]