摘要
目的通过整合药物代谢动力学数据进行多重药物靶点预测,探究止嗽散治疗咳嗽变异性哮喘(cough variant asthma,CVA)的作用机制。方法先利用大规模数据挖掘、文献检索搜集止嗽散方中所有中药的化学成分,再利用药物代谢动力学数据筛选其活性成分并用Swiss Target Prediction、SysDT和TargetNet方法进行靶点预测,并借助GeneCards和OMIM数据库获得CVA的致病基因,并与药物靶点取交集以构建蛋白相互作用网络,对获得的核心靶点进行生物学功能富集分析,最后选取若干核心靶点及其关键的成分进行分子对接验证。结果共筛出止嗽散治疗CVA的活性成分97个(包括白前苷元C、7,4′-二羟基黄酮、甘草酸、新对叶百部碱和β-谷甾醇)及靶点144个。通过分析蛋白相互作用网络得到MAPK3、TNF、CASP3、EGFR、PTGS2和MMP-9等10个核心靶点。KEGG富集分析得到30条与CVA相关的通路。分子对接验证核心靶点中EGFR、PTGS2和MMP-9与其关键化合物有较好结合力。结论止嗽散治疗CVA涉及多条信号通路,其分子机制可能是通过止嗽散中主要活性成分对PI3K-Akt、NF-κB和HIF-1等通路的调控,最终达到治疗CVA的效果。
Objective To investigate the mechanism of action of Zhisou Powder in the treatment of cough variant asthma(CVA)by integrating pharmacokinetic data and multiple drug target prediction.Methods Large-scale data mining and literature search were performed to collect the chemical components of Zhisou Powder.Pharmacokinetic data were used to screen out its active components,and the Swiss Target Prediction,SysDT,and TargetNet methods were used for target prediction.Meanwhile,GeneCards and OMIM databases were used to obtain the pathogenic genes of CVA,and the intersection of the pathogenic genes and the drug targets was obtained to construct a protein-protein interaction(PPI)network.A biological functional enrichment analysis was performed for the core targets obtained,and finally several core targets and their key components were selected for molecular docking validation.Results A total of 97 active components of Zhisou Powder were screened out for the treatment of CVA,including glaucogenin C,7,4′-dihydroxyflavone,glycyrrhizin,neotuberostemonine,and beta-sitosterol,and 144 targets were obtained.The PPI network analysis obtained 10 core targets such as MAPK3,TNF,CASP3,EGFR,PTGS2,and MMP-9,and the KEGG enrichment analysis obtained 30 pathways associated with CVA.The results of molecular docking validation showed that among these core targets,EGFR,PTGS2,and MMP-9 had good binding force to their key compounds.Conclusion The treatment of CVA by Zhisou Powder involves multiple signaling pathways,and Zhisou Powder exerts a therapeutic effect on CVA possibly by regulating the PI3K-Akt,NF-κB,and HIF-1 pathways through its main active components.
作者
陈丽君
阚红星
丁然
侯俊
杨银凤
CHEN Li-jun;KAN Hong-xing;DING Ran;HOU Jun;YANG Yin-feng(School of Medical Information Engineering, Anhui University of Chinese Medicine, Anhui Hefei 230012, China)
出处
《安徽中医药大学学报》
CAS
2021年第6期63-68,共6页
Journal of Anhui University of Chinese Medicine
基金
安徽中医药大学自然科学重点项目(2020zrzd15)
安徽中医药大学高层次人才引进项目(DT19200011)
国家自然科学基金项目(81904062)。
