目的 采用網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接技術(shù)研究黃芪甲苷抗抑郁的潛在作用機(jī)制。方法 通過GEO、DrugBank、TTD、DisGeNet、GeneCards數(shù)據(jù)庫(kù)獲得抑郁癥疾病靶點(diǎn)，檢索PharmMapper和SwissTargetPrediction數(shù)據(jù)庫(kù)獲得黃芪甲苷的預(yù)測(cè)靶點(diǎn)。使用R軟件Venn包獲取黃芪甲苷與抑郁癥的交集靶點(diǎn)基因，利用STRING網(wǎng)站與Cytoscape軟件獲得蛋白相互作用（PPI）網(wǎng)絡(luò)，并通過R軟件clusterprofile包對(duì)潛在作用靶點(diǎn)進(jìn)行基因本體論（GO）和京都基因與基因組百科全書（KEGG）富集分析；使用Autodock Vina 1.1.2軟件進(jìn)行分子對(duì)接。結(jié)果 黃芪甲苷治療抑郁癥的相關(guān)靶點(diǎn)共107個(gè)，主要為絲裂原活化蛋白激酶1（MAPK1）、表皮生長(zhǎng)因子受體（EGFR）和胱天蛋白酶3（CASP3）。這些核心靶點(diǎn)作用于鈣離子信號(hào)通路、MAPK信號(hào)通路、磷脂酰肌醇-3-羥激酶（PI3K）-蛋白激酶B（Akt）信號(hào)通路以及神經(jīng)活性配體–受體相互作用信號(hào)通路等發(fā)揮抗抑郁作用，分子對(duì)接顯示黃芪甲苷能與核心靶點(diǎn)均能較好的結(jié)合。結(jié)論 黃芪甲苷治療抑郁癥具有多靶點(diǎn)、多通路協(xié)同的特點(diǎn)，可通過改善細(xì)胞凋亡、促進(jìn)神經(jīng)再生、調(diào)節(jié)神經(jīng)炎癥以及調(diào)節(jié)單胺類神經(jīng)遞質(zhì)傳遞發(fā)揮協(xié)調(diào)抗抑郁作用。

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.

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