以网络药理学为基础探讨黄芩-厚朴治疗龋病的作用机制

Exploring the Mechanism of Scutellaria Baicalensis-Mangnolia Officinalis in Treating Dental Caries Based on Network Pharmacology

通过网络药理学和实验验证,探讨黄芩-厚朴治疗龋病的作用机制.从TCMSP中对黄芩-厚朴的药物成分及对应靶点进行研究,并通过Uniprot统一基因名称.使用Gene Cards、OMIM、Dis Genet获取龋病靶点,使用venny 2.1获取交叉靶点.使用STRING进行PPI分析,使用Cytoscape构建网络图.metscape用于GO和KEGG分析.使用Cytoscape软件构建“成分-靶点-通路”网络图.建立大鼠龋模型,用黄芩-厚朴汤局部治疗.检测核心靶蛋白在大鼠血清中的表达.结果发现黄芩-厚朴中32种有效成分可通过多种途径直接作用于31个疾病靶点,其中黄芩素、β-谷甾醇、豆甾醇、金合花、木质素、桉叶油素是核心成分,IL-6、AKT1、TNF、MMP9、VEGFA是最重要的靶点.基因功能注释分析结果显示,与重叠基因最可能相关的生物过程主要是炎症、细胞对生物刺激的反应,如细胞对脂多糖的反应,细胞组分主要涉及膜筏、进入管腔微区、细胞质膜等,分子功能主要涉及蛋白质二聚化、细胞因子活性、DNA结合转录因子和细胞因子受体等.通路富集分析结果提示黄芩-厚朴主要参与AGE-RAGE、TNF、IL-17、MAPK、JAK-STAT、HIF-1、VEGF、PI3K/AKT、凋亡等信号通路.黄芩-厚朴治疗后大鼠血清中IL6、AKT1、TNF、MMP9、VEGFA含量均升高.综上所述,黄芩-厚朴主要调控AGE-RAGE、TNF、IL-17、MAPK、JAK-STAT、HIF-1、VEGF、PI3K/AKT、凋亡等信号通路中的IL6、AKT1、TNF、MMP9、VEGFA等疾病靶点,干预酶活性、炎症反应等生物过程从而治疗龋病.

To explore the mechanism of Scutellaria baicalensis-Mangnolia officinalis in the treatment of dental caries through network pharmacology and experimental verification,the drug components and corresponding targets of Scutellaria baicalensis-Mangnolia officinalis were investigated from TCMSP,and the gene names were unified by Uniprot.GeneCards,OMIM,and DisGenet were used to obtain the disease targets of dental caries,and venny 2.1 was used to obtain the intersection targets.STRING was used for PPI analysis and Cytoscape was used to construct the network diagram.Metascape was used for GO and KEGG analysis.Cytoscape software was used to construct the"component-target-pathway"network diagram.The rat model of dental caries was established and treated with scutellaria baicalensis-mangnolia officinalis decoction by local treatment.The expression of core targets in rat serum was detected.Results showed that it was found that 32 active components in Scutellaria baicalensis-Mangnolia officinalis could directly act on 31 disease targets in the treatment of dental caries through multiple pathways,among which baicalein,β-sitosterol,stigmasterol.acacia,lignin,and eucalyptus olein were the core components,and IL6,AKT1,TNF,MMP9,and VEGFA were the most important targets.Gene functional annotation analysis results showed that the overlap genes most likely to be related to the biological process is mainly related to inflammation,cell response to biological stimulation,such as cell response to lipopolysaccharide,cell components mainly involved the membrane rafts,into the lumen of the micro area,cytoplasmic membrane,such as molecular function mainly involve protein dimerization,cytokine activity,DNA-binding transcription factors and cytokines receptors.The results of pathway enrichment analysis suggested that Scutellaria baicalensis-Mangnolia officinalis was mainly involved in AGERAGE,TNF,IL-17,MAPK,JAK-STAT,HIF-1,VEGF,PI3K/AKT,apoptosis and other signaling pathways.The contents of IL6,AKT1,TNF,MMP9 and VEGFA in serum of rats were increased after Scutellaria baicalensis-Mangnolia oficinalis treatment.In conclusion,Scutellaria baicalensis-Mangnolia officinalis mainly regulates IL6,AKT1,TNF,MMP9,VEGFA and other disease targets in AGE-RAGE,TNF,IL-17,MAPK,JAK-STAT,HIF-1,VEGF,PI3K/AKT,apoptosis and other signaling pathways,intervening the enzyme activity,inflammatory reaction and other biological processes to treat dental caries.