机构地区:[1]湖南中医药大学,长沙410208
出 处:《中药药理与临床》2024年第5期48-56,共9页Pharmacology and Clinics of Chinese Materia Medica
基 金:湖南省自然科学基金项目(编号:2021JJ30506);湖南省教育厅重点项目(编号:21A0242);湖南省大学生创新创业训练计划-省级项目(编号:S202210541130)。
摘 要:目的:利用网络药理学和实验验证探究三七总皂苷活性成分调控铁死亡干预口腔黏膜下纤维化的药效物质基础、潜在靶标及作用机制。方法:结合前期研究,通过文献检索确定网络药理学分析的三七总皂苷中的候选有效成分,并通过PubChem(有机小分子生物活性数据库,http://pubchem.ncbi.nlm.nih.gov)检索有效成分,使用GeneCards数据库获得三七总皂苷活性成分的对应靶基因。在GeneCards、OMIM数据库中搜集口腔黏膜下纤维化的相关靶点。将三七总皂苷活性成分与口腔黏膜下纤维化的交集靶点通过Cytoscape 3.7.0软件绘制相应“活性成分-作用靶点”网络,并借助CytoHubba插件获得三七总皂苷活性成分的度值(Degree)排名,并对关键核心靶点进行分析。基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析通过DAVID数据库进行。将三七总皂苷活性成分干预口腔黏膜下纤维化的靶基因与通过FerrDb数据库获取得到的铁死亡过程中的标记基因及调控因子取交集,获得通过调控铁死亡过程干预口腔黏膜下纤维化的三七总皂苷靶基因。利用AutoDockTool1.5.7软件进行化合物和核心靶点的分子对接。人永生化角质形成细胞(HaCaT细胞系)体外培养后分为空白对照组、模型对照组、三七总皂苷12.5、25、50μg/mL组;各组在相应不含药或含药的完全培养液中培养24 h后收集细胞;采用Western blot法检测各组细胞Ⅰ型胶原(COL-I)、低氧诱导因子-1(HIF-1α)、轻链溶质载体家族7成员11(SLC7A11)、谷胱甘肽过氧化物酶4(GPX4)蛋白表达;透射电镜观察细胞线粒体形态学变化。结果:共筛选出三七总皂苷中5个活性成分,包括人参皂苷Rb1、人参皂苷Rg1、人参皂苷Rd、三七皂苷R1和人参皂苷Re,以及前列腺素内过氧化物合酶2(PTGS2)、一氧化氮合酶2(NOS2)等20个作用靶标。三七总皂苷中的5个活性成分与RNA聚合酶II启动子对pri-mObjective:To explore the pharmacodynamic material basis,potential targets and mechanism of Panax notoginseng saponins in regulating ferroptosis for intervention in oral submucous fibrosis by network pharmacology and experimental research.Methods:Combined with previous studies,the candidate active components of Panax notoginseng saponins for network pharmacological analysis were identified through literature search,and the active ingredients were retrieved by Pub Chem(organic small molecule bioactivity database,http://pubchem.ncbi.nlm.nih.gov).The target genes of Panax notoginseng saponins were obtained from GeneCards database.The related targets of oral submucosal fibrosis were collected from GeneCards and OMIM databases.The intersection targets of Panax notoginseng saponins and oral submucous fibrosis were visualized as an"active ingredient-target"network using Cytoscape 3.7.0 software.The degree of active components of Panax notoginseng saponins was obtained by CytoHubba plug-in,and the key core targets were analyzed.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were conducted through the DAVID database.The target genes of Panax notoginseng saponins active components that intervene in oral submucous fibrosis intersected with the marker genes and regulatory genes in the process of ferroptosis obtained through FerrDb database,and the target genes of Panax notoginseng saponins interfering in oral submucous fibrosis by regulating the process of ferroptosis were obtained.Molecular docking of the compounds and core targets was performed using AutoDockTool1.5.7 software.HaCa T cells were cultured in vitro and divided into normal control group,model control group,Panax notoginseng saponins 12.5μg/mL,25μg/mL and 50μg/mL groups.After 24 hours of incubation in the respective culture media with or without Panax Notoginseng Saponins,cells were collected.The protein expression levels of collagen-Ⅰ(COL-I),hypoxa-inducing faction-1(HIF-1α),solute carrier family 7 m
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