巴戟天-苍术药对治疗青少年抑郁症的网络药理学研究

Network Pharmacology Research on Radix Morindae Officinalis-Rhizoma Atractylodis Herb Pair in the Treatment of Adolescent Depression

目的采用网络药理学方法,探讨巴戟天-苍术治疗青少年抑郁症的作用机制。方法通过中草药系统药理学平台(TCMSP)筛选出药对巴戟天-苍术的有效成分及作用靶点。利用String数据库构建药物成分靶点蛋白相互作用(PPI)网络。从OMIM、DrugBank、TTD、GeneCards数据库检索与青少年抑郁症相关的靶点,并得到疾病与药物的靶点映射。采用Cytoscape 3.7.2软件对核心靶点进行拓扑分析,利用AutoDock软件将关键靶点及主要活性成分进行分子对接。最后利用DAVID数据库进行GO生物过程分析和KEGG通路富集分析。结果筛选出巴戟天-苍术有效成分20种,作用靶点242个,疾病靶点366个。核心靶点主要包括AKT1、MAPK3、MAPK1、TP53、APP、GAPDH、CXCL8、ALB、IL-6、SRC等。分子对接显示,汉黄芩素和β-谷甾醇与主要活性成分的结合能均<-5.0 kJ·mol^-1,其中β-谷甾醇与核心靶点GAPDH结合能最好。涉及与青少年抑郁症相关的GO分析82个条目,主要涉及蛋白结合、质膜、核质、线粒体等。KEGG有46条富集通路与治疗青少年抑郁症相关,主要包括神经活性配体-受体相互作用、多巴胺能突触、5-羟色胺能突触、MAPK信号通路、雌激素信号通路、TNF信号通路等,涉及信号传导、神经系统、内分泌系统等多方面通路。结论巴戟天-苍术药对可能通过参与神经可塑性、信号传导、激素调节及抗炎等功能治疗青少年抑郁症。

Objective To explore the action mechanism of Radix Morindae Officinalis-Rhizoma Atractylodis herb pairinthe treatment of adolescent depression by usingnetwork pharmacology.Methods The effective components and targets of Morindae Officinalis-Rhizoma Atractylodis were screened by Chinese herbal medicine system pharmacology platform(TCMSP),and the PPI network of target protein of herb ingredients was constructed by using String database.The targets related to adolescent depression were retrieved from OMIM,DrugBank,TTD and GeneCards databases,and the mapping of disease and drug targets was obtained.Cytoscape 3.7.2 software was used for topological analysis of the core targets.The key targets and main active components weremolecular docked by AutoDock software.Finally,DAVID database was used for GO biological process analysis and KEGG pathway enrichment analysis.Results A total of 20 active components,242 targets and 367 disease targets of Radix Morindae Officinalis-Rhizoma Atractylodis were screened.The core targets mainly included AKT1,MAPK3,MAPK1,TP53,APP,GAPDH,CXCL8,ALB,IL-6,SRC,etc.Molecular docking showed that the binding energy of wogonin and β-sitosterol with the main active components was <-5.0 kJ·mol^-1,and β-sitosterol had the best binding energy with the core target GAPDH.GO analysis involved 82 items related to adolescent depression,mainly involving protein binding,plasma membrane,nuclear cytoplasm,mitochondria,etc.46 enrichment pathways of KEGG wererelated to the treatment of adolescent depression,mainly including neuroactive ligand-receptor interaction,dopaminergic synapses,5-hydroxytryptaminergic synapses,MAPK signaling pathway,estrogen signaling pathway,TNF signaling pathway,etc.,involving signal transduction,nervous system,endocrine system and other pathways.Conclusion Radix Morindae Officinalis-Rhizoma Atractylodisherb pair may treatadolescent depression by participating in neuroplasticity,signal transduction,hormone regulation and anti-inflammatory functions.