基于网络药理学探讨绞股蓝治疗阿霉素心肌病的药效物质基础和分子机制  

Investigation of the pharmacodynamic material basis and molecular mechanism of gynostemma pentaphyllum in the treatment of adriam‐ycin cardiomyopathy based on network pharmacology

作　　者：魏薇 张继婕 刘中艺 高思[2] WEI Wei;ZHANG Jijie;LIU Zhongyi;GAO Si(College of Science,Guangxi University of Science and Technology,Liuzhou 545006,China;Medical School,Guangxi University of Science and Technology,Liuzhou 545006,China)

机构地区：[1]广西科技大学理学院,广西柳州545006 [2]广西科技大学医学部,广西柳州545006

出　　处：《广西科技大学学报》2021年第4期111-118,共8页Journal of Guangxi University of Science and Technology

基　　金：国家自然科学基金青年科学基金项目(81500214);广西科技大学研究生教育创新计划项目(GKYC202124)资助.

摘　　要：采用中药网络药理学方法探讨绞股蓝治疗阿霉素心肌病的药效物质基础和潜在作用机制.通过检索TC‐MSP、SymMap、TCMID数据库平台获取绞股蓝的候选药效成分,并借助Uniprot数据库获取候选药效成分的潜在作用靶点;采用Cytoscape 3.8.1软件构建有效成分-靶点蛋白相互作用网络图;运用Genecards、OMIM数据库筛选阿霉素心肌病的疾病相关靶点,结合String数据库绘制药物-疾病基因的蛋白互作网络;采用Metascape数据库对交集靶标进行基因功能分析(GO)及KEGG通路富集分析,对绞股蓝改善阿霉素心肌病的作用机制作出合理推测.共筛选出绞股蓝有效活性成分26个,包括槲皮素、谷甾醇、绞股蓝皂苷等,活性成分发挥作用的潜在靶标有89个,主要有TNF-α、TP53、AKT1、IL-6等;靶点参与的功能主要有氧化应激、凋亡调控、炎症因子刺激反应、蛋白质丝氨酸/苏氨酸激酶活性调节等,主要富集通路有p53、TNF-α、PI3K-Akt、AMPK等信号通路,以及线粒体自噬和细胞钙调控通路等.结果表明,绞股蓝中槲皮素、谷甾醇、绞股蓝皂苷等有效活性成分能够通过调节p53、TNF-α、Akt、AMPK等信号分子,参与细胞程序性死亡、氧化应激和线粒体稳态调控,从而达到防治阿霉素心肌病的目的.This study was to explore the pharmacodynamic basis and potential mechanism of gynostemma pentaphyllum in the treatment of doxorubicin cardiomyopathy by using network pharmacology of Chinese medicine.The candidate pharmacological components of gynostemma pentaphyllum were obtained by retrieving TCMSP,SYMMAP,TCMID data platforms,and the potential action targets of candidate pharmacological components were obtained by Uniprot database.Cytoscape 3.8.1 software was used to construct the active component-target protein interaction network diagram.GeneCards and OMIM databases were used to screen out disease-related targets of doxorubicin cardiomyopathy,and the protein interaction network of drug-disease genes was drawn by combining the String database.Metascape database was used for gene function analysis(GO)and KEGG pathway enrichment analysis of the intersection targets,so as to make a reasonable prediction on the mechanism of gynostemma pentaphylum improving doxorubicin cardiomyopathy.Atotal of 26 active components of gynostemma pentaphyllum related to adriamycin cardiomyopathy were screened out,including quercetin,sitosterol,gynostemma pentaphyllum saponins,etc.,and 89 potential targets of active components were identified,mainly including TNF-α,TP53,ATK1,IL-6,etc.The main functions involved in the target included oxidative stress,apoptosis signal,inflammatory cytokine stimulation response,regulation of protein serine/threonine kinase activity,etc.The main enrichment pathways included p53,TNF-α,PI3K-Akt,AMPK and other signaling pathways,as well as mitochondri‐al autophagy and cellular calcium signal transduction pathways.The results showed that quercetin,sitosterol,gypenoside and other active components of gynostemma pentaphyllum could regulate p53,TNF-α,Akt,AMPK and other signaling molecules to participate in the regulation of programmed cell death,oxidative stress and mitochondrial homeostasis,so as to achieve the purpose of prevention and treatment of doxorubicin cardiomyopathy.

关 键 词：绞股蓝 网络药理学 阿霉素心肌病 药效物质基础 分子机制 

分 类 号：R282.710.5[医药卫生—中药学] R259.422[医药卫生—中医学]