目的 利用网络药理学及分子对接技术探究柴胡-香附药治疗抑郁症(Depression)的活性成分及潜在作用机制,为进一步研究柴胡-香附治疗抑郁症的作用机制提供部分理论基础和参考思路.方法 通过中药系统药理学数据库与分析平台(TCMSP)检索柴胡、香附活性成分及靶点;利用人类基因数据库(Gene Cards)、在线人类孟德尔遗传(Online Mendelian Inheritance in Man,OMIM)数据库查找疾病靶点;借助STRIING数据库及Cytoscape3.9.1软件构建药物活性成分-交集靶点网络,进行蛋白相互作用(PPI)网络分析;利用Metascape数据库对靶点进行通路富集分析;利用基因数据库(GEO)获取人类抑郁症差异基因后,将最终得到的交集核心靶点运用Pymol软件进行分子对接验证,证实药物对靶点的作用.结果 筛选得到柴胡-香附药的有效成分25种(共同成分4种).GEO分析得到1217个抑郁症差异基因,与核心通路对应的67个核心基因交集后得到药物治疗人类抑郁症核心靶标5个,分别为丝裂原活化蛋白激酶14(MAPK14)、基质金属蛋白酶9(MMP9)、表皮生长因子(EGF)、MYC癌基因(MYC)及单胺氧化酶A(MAOA).分子对接显示关键靶点与核心成分大多可形成稳固结构.结论 柴胡-香附对抑郁症可能通过MAPK14、MMP9、EGF、MYC及MAOA等靶点来实现药效作用.
Exploring the mechanism of action of bupleurum-cyperus rotundus in treating depression based on net-work pharmacology and molecular docking techniques
Objective Employing network pharmacology,GEO analysis,and molecular docking methods to explore the active constituents and underlying mechanisms of bupleurum-cyperus rotundus medicine in treating depres-sion,thus laying a partial theoretical groundwork and offering directional guidance for future research on its mechanism.Methods Active components and associated targets of Bupleurum and Cyperus rotundus were identified and screened using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and String da-tabases;The Human Gene Database(GeneCards)and Online Mendelian Inheritance in Man(OMIM)databases were employed to pinpoint depression-related targets.Once we identified the common targets of the disease and drug,the String platform and Cytoscape 3.9.1 software were employed to construct a network symbolizing these overlapping tar-gets and active elements.This network was then evaluated using Protein-Protein Interactions(PPI)network analysis.Through bioinformatics analysis of selected datasets from m the Gene Expression Database(GEO),genes exhibiting differences in human depression were identified.Intersection of these genes with core targets associated with key path-ways was performed to validate the target's reliability in clinical specimens.This led to the identification of primary tar-gets for treating depression clinically.Molecular docking studies were then executed using Pymol software to affirm the drug's efficacy on the identified targets.Results In the Bupleurum-Cyperus medication,25 active constituents were identified,four of which were common components,which interact with 123 depression-related targets.GEO analysis yielded 1217 differential genes for depression,and after intersecting with 67 core genes corresponding to key pathways,five core targets were identified for the treatment of human depression using Bupleurum-Cyperus medicine,namely Mi-togen activated protein kinase 14(MAPK14),Matrix metalloproteinase 9(MMP9),Epidermal Growth Factor(EGF),MYC proto-oncogene(MYC),and Monoamine oxidase A(MAOA).Molecular docking indicated that the key targets form stable structures with most of the core components.Conclusion Bupleurum-cyperus rotundus may exert its ther-apeutic impact on depression through the key targets of MAPK14,MMP9,EGF,MYC,and MAOA.
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