基于BATMAN-TCM在线分析平台的浙贝母-瓜蒌配伍治疗慢性阻塞性肺病的网络药理学研究

Network pharmacology study of Fritillariae Thunbergii Bulbus-Trichosanthis Fructus compatibility for treating chronic obstructive pulmonary disease based on the BATMAN-TCM online analysis platform

基于中药分子机理的生物信息学分析工具(bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine,BATMAN-TCM)挖掘浙贝母-瓜蒌治疗慢性阻塞性肺病的分子作用机制。应用BATMAN-TCM预测浙贝母-瓜蒌的潜在靶点,GeneCards数据库检索慢性阻塞性肺病的靶点;应用Cytoscape 3.7.1软件构建化合物-疾病-靶点相互作用网络、蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络,进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)的生物通路富集分析。结果筛选得到浙贝母-瓜蒌中21种活性成分,基于STRING构建的浙贝母-瓜蒌靶点PPI网络包含131个节点和236条相互作用关系,关键节点包括ANXA1、EDN1、HDAC1、RXRA、ADRA2A、OXT、RXRB等。GO富集分析途径主要涉及离子门控通道活性、底物特异性通道活性、被动跨膜转运活性、细胞外配体门控离子通道活性、神经递质受体活性、配体门控离子通道活性等。KEGG通道分析主要涉及神经活动配体-受体相互作用、cAMP信号通路、钙离子信使通路、类胆碱能突触、逆行内源性大麻素信号传导、5-羟色胺能突触、多巴胺能突触等途径。研究结果提示浙贝母-瓜蒌关键的作用靶点包括ANXA1、HDAC1等,信号通路方面涉及类胆碱能、5-羟色胺、多巴胺等神经受体相关通路,体现了中药复方的整体性特点,为进一步研究浙贝母-瓜蒌的分子作用机制提供了新思路。

Based on the bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine(BATMAN-TCM),this study revealed the molecular mechanism of action of Fritillariae Thunbergii Bulbus-Trichosanthis Fructus(FTB-TF)for treating chronic obstructive pulmonary diseases(COPD).The BATMAN-TCM was adopted to predict the potential targets of FTB-TF,whereas the GeneCards database was used to search the targets of COPD.Cytoscape 3.7.1 software was used to construct a compound-disease-target interaction network and protein-protein interaction(PPI)network to conduct gene ontology(GO)enrichment analysis and pathway enrichment analysis based on the Kyoto encyclopedia of genes and genomes(KEGG).A total of 21 types of active ingredients were screened from FTB-TF,and the compound-disease-target network was constructed.The PPI network of FTB-TF targets was established based on STRING,and it included 131 nodes and 236 edges.Examples of the key nodes included ANXA1,EDN1,HDAC1,RXRA,ADRA2A,OXT,and RXRB.The GO enrichment analysis mainly involved ion-gated channel activity,substrate-specific channel activity,passive transmembrane transporter activity,extracellular ligand-gated ion channel activity,neurotransmitter receptor activity,and ligand-gated ion channel activity.The KEGG pathway analysis mostly involved neuroactive ligand-receptor interaction,cAMP signaling pathway,calcium signaling pathway,cholinergic synapse,retrograde endocannabinoid signaling,serotonergic synapse,and dopaminergic synapse.The results suggested that ANXA1 and HDAC1,for instance,were the key targets of FTB-TF.The signaling pathways primarily involved neuroreceptor pathways such as acetylcholine,serotonin,and dopamine.These findings reflected the overall characteristics of the Chinese medicine compound prescription,thereby providing new clues for further research on the molecular mechanism of action of FTB-TF.