基于数据挖掘和网络药理学探讨川贝母治疗肺系疾病的核心中药和机制

Explore the Core Chinese Medicine and Mechanism of Fritillariae Cirrhosae Bulbus in the Treatment of Pulmonary Diseases Based on Data Mining and Network Pharmacology

基于数据挖掘川贝母治疗肺系疾病的核心中药和基于网络药理学探讨“川贝母-人参”治疗肺系疾病之支气管哮喘的作用机制。通过数据处理软件,利用统计学方法对所收集的含贝母肺系疾病中药组方进行频数统计、关联规则分析和聚类分析。并利用网络药理学知识对核心药对治疗肺系典型疾病支气管哮喘进行靶点收集筛选、基因本体论(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)富集分析,最后利用分子对接验证。共筛选出含贝母处方420个,涉及中药463味;高频药物有甘草、杏仁等;聚类分析可得8类;高频核心二联药物组合有“川贝母-阿胶”“川贝母-人参”等,三联药物组合包括“川贝母-天冬-麦冬”“川贝母-天冬-甘草”等,四联药物组合“川贝母-桑白皮-桔梗-甘草”“川贝母-桑白皮-杏仁-甘草”等;由于阿胶为动物药材,则分析“川贝母-人参”药对治疗作为治疗支气管哮喘这一典型肺系疾病的核心药对,其中Hub靶点包括“AKT1”“PTGS2”等;核心活性成分包括“beta-sitosterol”“kaempferol”等;预测跟脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化、弓形虫病、糖尿病并发症中的高级糖基化终末产物-受体(advanced glycation end products-receptor for AGE,AGE-RAGE)信号通路有关,在分子对接中高频活性药物成分Fumarine与疾病靶点的PTGS2最为紧密。基于统计学方法和网络药理学技术,川贝母常与人参等配伍使用治疗肺系疾病,且药物的活性成分会利用相关AKT1等靶点和脂质和动脉粥样硬化等通路起到治疗作用;本研究揭示了含川贝母治疗肺系疾病方剂潜在的一些规律,为进一步开放川贝母组方药物提供了思路。

To explore the mechanism of“Fritillariae Cirrhosae Bulbus-Ginseng”in treating bronchial asthma of lung diseases based on data mining and network pharmacology.By means of data processing software,frequency statistics,association rule analysis and cluster analysis were carried out for the collected Chinese herbal prescriptions containing fritillaria for pulmonary diseases.Target collection and screening,GO(gene ontology)function analysis and KEGG(Kyoto encyclopedia of genes and genomes)pathway enrichment analysis of the core drug pair for treating bronchial asthma,a typical disease of the lung system,were conducted by using network pharmacology knowledge,and finally molecular docking verification was conducted.A total of 420 prescriptions containing fritillaria were screened,involving 463 TCM.High frequency drugs have glycyrrhiza,Bitter Apricot Seed,etc.8 categories can be obtained by cluster analysis.The high-frequency core two-drug combination includes“Fritillariae Cirrhosae Bulbus-Collacoriiasini”and“Fritillari-ae Cirrhosae Bulbus-Ginseng”,the three-drug combination includes“Fritillariae Cirrhosae Bulbus-Radix asparagi-Radix Ophiopogo-nis”and“Fritillariae Cirrhosae Bulbus-Radix asparagi-glycyrrhiza”,and the four-drug combination“Fritillaria Cirrhosae Bulbus-Mori Cortex-Platycodon grandifloras-glycyrrhiza”and“Fritillaria Cirrhosae Bulbus-Mori Cortex-Bitter Apricot Seed-glycyrrhiza”.Since Col-lacoriiasini is an animal medicinal material,it was analyzed that the“Fritillariae Cirrhosae Bulbus-Ginseng”drug pair was used as the core drug pair in the treatment of bronchial asthma,a typical pulmonary disease,in which Hub targets included“AKT1”,“PTGS2”,etc.Core active ingredients include“beta-sitosterol”,“kaempferol”,etc.The prediction is related to AGE-RAGE signaling pathways in lipid and atherosclerosis,fluid shear stress and atherosclerosis,toxoplasmosis,and diabetes complications.In molecular docking,the high frequency active drug ingredient Fumarine is most closely associated with PTGS2 of disease targets.Based on statistical meth-ods and network pharmacological techniques,Fritillariae Cirrhosae Bulbus is often used in combination with ginseng for the treatment of pulmonary diseases,and the active ingredients of the drug will use related AKT1 targets and lipid and atherosclerosis pathways to play a therapeutic role.This study revealed some potential rules of Fritillariae Cirrhosae Bulbus prescription for the treatment of lung disea-ses and provided ideas for further opening the Fritillariae Cirrhosae Bulbus prescription.