[关键词]
[摘要]
目的 采用网络药理学和分子对接技术研究黄芪甲苷抗抑郁的潜在作用机制。方法 通过GEO、DrugBank、TTD、DisGeNet、GeneCards数据库获得抑郁症疾病靶点,检索PharmMapper和SwissTargetPrediction数据库获得黄芪甲苷的预测靶点。使用R软件Venn包获取黄芪甲苷与抑郁症的交集靶点基因,利用STRING网站与Cytoscape软件获得蛋白相互作用(PPI)网络,并通过R软件clusterprofile包对潜在作用靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析;使用Autodock Vina 1.1.2软件进行分子对接。结果 黄芪甲苷治疗抑郁症的相关靶点共107个,主要为丝裂原活化蛋白激酶1(MAPK1)、表皮生长因子受体(EGFR)和胱天蛋白酶3(CASP3)。这些核心靶点作用于钙离子信号通路、MAPK信号通路、磷脂酰肌醇-3-羟激酶(PI3K)-蛋白激酶B(Akt)信号通路以及神经活性配体–受体相互作用信号通路等发挥抗抑郁作用,分子对接显示黄芪甲苷能与核心靶点均能较好的结合。结论 黄芪甲苷治疗抑郁症具有多靶点、多通路协同的特点,可通过改善细胞凋亡、促进神经再生、调节神经炎症以及调节单胺类神经递质传递发挥协调抗抑郁作用。
[Key word]
[Abstract]
Objective To investigate the potential mechanisms of astragaloside IV in treatment of depression by using network pharmacology and molecular docking. Methods The targets gene of depression disease were obtained through GEO, DrugBank, TTD, DisGeNet, and GeneCards database, predicted targets of astragaloside IV were explored by searching the PharmMapper and SwissTargetPrediction database. Intersection of the targets of astragaloside IV and depression were obtained by Venn package of R software. Potential targets protein interaction network was analyzed using STRING website and Cytoscape 3.9.0 software. The KEGG and GO enrichment analysis were performed using the R software clusterprofile package and molecular docking was performed by AutoDock Vina1.1.2 software. Results There were 107 related targets of astragaloside IV in treatment of depression, mainly including MAPK1, EGFR, CASP3, etc. These core targets act on calcium ion signaling pathway, MAPK signaling pathway, phosphatidylinositol-3-hydroxykinase (PI3K) -protein kinase B (Akt) signaling pathway and neural active ligand-receptor interaction signaling pathway to play an antidepressant effect. Molecular docking showed that astragaloside IV could bind well with the core targets. Conclusion Astragaloside IV can exert a synergistic antidepressant effect through multi-targets and multi-pathways improving cell apoptosis, promoting neural regeneration, regulating neuroinflammation and monoamine neurotransmitter transmission, which can provide a basis for the follow-up study.
[中图分类号]
R285
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