基于网络药理学探究黄连治疗慢性牙周炎伴牙龈卟啉单胞菌感染的作用机制

The mechanism of coptis in treating chronic periodontitis with porphyromonas gingivalis infection based on network pharmacology

目的为了探究黄连治疗牙龈卟啉单胞菌相关性慢性牙周炎作用机制,本研究利用网络药理学方法分析黄连的主要活性化合物、潜在靶点和相关通路。方法运用中药系统药理学分析平台(TCMSP)对黄连的药物活性化合物及药物作用靶点基因进行筛选。通过GeneCards数据库收集疾病相关靶点,对药物作用靶点及疾病相关靶点进行韦恩分析,确定药物作用潜在靶点;应用Cytoscape3.6.1软件以及String数据库分别构建“药物-化合物-潜在靶点”相互作用网络及蛋白相互作用(PPI)网络图。运用DAVID数据库对关键靶点进行基因本体(GO)功能,京都基因及基因组百科全书(KEGG)通路富集分析。结果黄连中槲皮素、小檗碱和小檗红碱等9种药物是黄连治疗牙龈卟啉单胞菌相关性慢性牙周炎的活性化合物,其作用机制涉及IL-1β、IL-6等47个潜在靶点以及TNF-α信号通路。经生物信息学验证,最终筛选出5个在牙周炎患者牙龈组织中上调的靶点,其中以黄连碱的结合能最低。结论黄连治疗慢性牙周炎伴牙龈卟啉单胞菌感染,是通过多成分、多靶点、多途径发挥其抑菌、抗炎、调控炎症进展的作用,这为使用传统中药治疗慢性牙周炎奠定一定的理论基础。

Objective To investigate the mechanism of coptis in treating chronic periodontitis associated with porphyromonas gingivalis,network pharmacology was used to analyze the main active compounds,otential targets and related pathways of coptis.Methods The drug active compounds and drug target genes of coptis were screened by TC-MSP.Disease-related targets were collected through GeneCards database,and Wayne analysis was performed on active targets and disease-related targets to identify potential genes.Cytoscape3.6.1 software and String database were used to construct the drug-compound-potential target interaction network and protein interaction(PPI)network.DAVID database was used to perform gene ontology(GO)function,Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for key targets.After bioinformatics verification,five targets were finally screened for up-regulation in the gingival tissue of periodontitis patients,among which berberine had the lowest binding energy.Results 9 drug active compounds including quercetin and berberine were selected,involving 47 potential targets such as IL-1β,IL-6 and TNF-αsignaling pathway.Conclusions Coptis in the treatment of chronic periodontitis accompanied by porphyromonas gingivalis infection can play the role of antibacterial,anti-inflammatory and regulation of inflammatory progression through multi-component,multi-target and multi-pathway.