基于网络药理学和分子对接技术探索小儿化积止咳方对痰证的作用机制

Studies on the mechanism of Xiaoer Huaji Zhike Formula to expectorant

基于网络药理学和分子对接技术探讨小儿化积止咳方对痰证的作用机制。通过中草药系统药理学平台数据库(TCMSP)、小分子药物靶点预测在线平台数据库(Swiss Target Prediction)和药物银行数据库(DrugBank)收集小儿化积止咳方的有效成分、靶点以及痰证相关的靶点。通过韦恩2.1.0(Venny 2.1.0)和蛋白质-蛋白质互作(PPI)分析筛选出枢纽基因(hub genes),并进一步对hub genes进行生物功能注释(GO)和京都基因和基因组百科全书(KEGG)分析,最后使用分子对接技术验证药物与hub genes产物蛋白的亲和力。结果表明:最终筛选出10个hub genes,分别是CYP2D6、MAOA、SLC6A2、ADRB2、DRD1、ADRB1、SLC6A4、CHRM1、SLC6A3和CYP3A4,其中ADRB2、MAOA、CYP3A4、SLC6A2、CHRM1和DRD1通过与豆固醇、17-β-雌二醇、stock1n-53032和丁香酚靶向结合,来调节神经活性配体-受体的相互作用、钙信号通路,并由此达到化积止咳祛痰的功效。研究表明:小儿化积止咳方作为中药组分,具有多成分、多靶点和多途径的特点,网络药理学和分子对接技术初步揭示了小儿化积止咳方的作用机制,并为其组方改进提供了理论依据。

The mechanism of action was explored for a traditional Chinese medicine Xiaoer Huaji Zhike Formula(XEHJZKF)on phlegm syndrome using the network pharmacology and molecular docking techniques.The active ingredients and targets of XEHJZKF,as well as the phlegm-related targets were identified through TCMSP,Swiss Target Prediction,and DrugBank databases.The hub genes,determined by Venny 2.1.0 and PPI analysis,were further investigated according to biofunctional annotation(GO)and KEGG.Subsequently,the affinity of the drugs with the product proteins from the hub genes was verified using molecular docking techniques.Among the 10 hub genes,namely CYP 2 D 6,MAOA,SLC 6 A 2,ADRB 2,DRD 1,ADRB 1,SLC 6 A 4,CHRM 1,SLC 6 A 3 and CYP 3 A 4,six of them(ADRB 2,MAOA,CYP 3 A 4,SLC 6 A 2,CHRM 1 and DRD 1)showed the regulation of the neuroactive ligand-receptor interaction and calcium signaling pathway through the binding with stigmasterol,17-beta-estradiol,stock1n-53032,and eugenol,which ultimately led to the effect of resolving accumulation and relieving cough and expectoration.Our research on XEHJZKF demonstrated its multi-component,multi-target,and multi-pathway characteristics,and further studies on its mechanism of action provided a theoretical basis for future formulation improvement.