基于网络药理学研究蒙药棘豆止咳散主治“痰、咳、喘”作用机制

Mechanism on Stopping Cough,Removing Sputum and Calming Asthma Effects of Jidou Zhike Powder Based on Network Pharmacology

目的:观察棘豆止咳散止咳、化痰和平喘作用,利用网络药理学研究方法筛选棘豆止咳散的活性成分,寻找其止咳、化痰和平喘的核心靶点,探讨其作用机制。方法:先采用浓氨水致小鼠咳嗽实验、小鼠气管段酚红排泌实验、磷酸组胺诱发小鼠哮喘实验考察棘豆止咳散止咳、化痰和平喘作用,再利用TCMSP、Swiss Target Prediction等数据库挖掘棘豆止咳散有效成分并预测其作用靶点,通过DisGeNET和DrugBank数据库中检索止咳、化痰和平喘的相关靶点,取两者靶点交集,利用STRING数据库构建PPI网络;通过DAVID进行GO功能富集和KEGG通路富集分析,最后利用Cytoscape3.7.2软件构建化合物-靶点-通路网络图。结果:与对照组比较,棘豆止咳散高剂量组咳嗽次数显著减少(P<0.05),中剂量组与高剂量组咳嗽潜伏期显著延长(P<0.05,P<0.01);高剂量组吸光度(A)值明显增加(P<0.05);中剂量组引喘潜伏期(S)值明显增加(P<0.05),高剂量组引喘潜伏期(S)值明显增加(P<0.01)。棘豆止咳散中有111个活性成分、46个作用靶点与止咳、化痰和平喘相关,通过GO功能富集和KEGG通路富集分析收集到530条BP条目、32条CC条目、25条MF条目,16条KEGG信号通路;按Degree值和BC值大小排序发现quercetin、luteolin、apigenin、kaempferol等为核心成分,PTGS2、NOS2、ADRB2、TNF等为核心靶点。结论:该研究体现了蒙药棘豆止咳散有止咳、化痰和平喘作用,及多成分-多靶点-多途径的作用特点,该研究还为棘豆止咳散止咳、化痰和平喘的作用机制提供了新的思路,为后续机制验证实验指明了方向。

Objective:To observe the effects of stopping cough,removing sputum and calming asthma of Jidou Zhike Powder,and to predict the action targets of active ingredients to understand the“multi-components,multi-targets,and multi-pathways”mechanism.Methods:The antitussive,expectorantant and antiasthmatic effects of Jidou Zhike powder were studied by the cough model of mice caused by concentrated ammonia,phenol red excretion in tracheal segment model of mice,and asthma model of mice induced by histamine phosphate.Target proteins related with cough,sputum and asthma were selected through mining literatureand retrieving in DisGeNET and DrugBank database,and the main active components and potential target proteins from Jidou Zhike Powder were computedand analyzed by DAVID and Cytoscape 3.7.2 to build a molecular-protein regulatory network.Results:Compared with the control group,the number of coughs in the high-dose group of Jidou Zhike powder was significantly reduced(P<0.05),and the cough incubation period in the middle-dose group and the high-dose group was significantly extended(P<0.05,P<0.01).Compared with the control group,the high-dose group of Jidou Zhike powder significantly increased the absorbance(A)value(P<0.05).Compared with the control group,the incubation latency(S)values of the middle and high dose groups of Jidou Zhike powder were significantly increased(P<0.05,P<0.01).According to the combined with database retreival and literature search,111 candidate active molecules,46 corresponding target,and 16 signal pathways in Jidou Zhike Powder were screened out.Conclusion:Stopping cough,removing sputum and calming asthma effects of JIdou Zhike Powder showed the characteristics of traditional Mongolian medicine in multi-components,multi-targets,and multi-pathways.This research provides a scientific basis for elucidation of the action mechanism of stopping cough,removing sputum and calming asthma effects of Jidou Zhike Powder.