基于网络药理学和分子对接技术探究酸枣仁汤抗抑郁作用机制

Study on the antidepressant mechanism of Suanzaoren Decoction based on network pharmacology and molecular docking

目的:基于网络药理学和分子对接技术探究酸枣仁汤抗抑郁的主要作用机制。方法:采用中药系统药理学数据库和分析平台(TCMSP)检索酸枣仁汤的活性成分靶点。通过Drugbank、GeneCards、OMIM等数据库检索抑郁症相关靶点,获得成分靶点和疾病靶点的交集,利用STRING数据库构建酸枣仁汤成分靶点与抑郁症靶点的蛋白质-蛋白质相互作用(PPI)网络。利用Metascape数据库进行GO富集分析和KEGG富集分析。采用AutoDock 4.2软件进行分子对接研究。结果:根据药动学参数OB、BBB、DL筛选出90种活性成分,其中主要活性成分为(S)-Coclaurine(左旋乌药碱),7-Methoxy-2-methyl isoflavone(7-甲氧基-2-甲基异黄酮)、Formononetin(刺芒柄花素)、Licochalcone A(甘草查尔酮A)、Anhydroicaritin(脱水淫羊藿素)、Hederagenin(常春藤皂苷元)、Myricanone(杨梅酮)等。获得成分靶点与疾病靶点的交集63个,关键靶点为AKT1、NOS3、PTGS2、MAPK1、CHRM2等。药物作用机制与PI3K-Akt、cAMP、TNF等信号通路相关。分子对接技术验证表明酸枣仁汤中主要活性成分与关键靶点分子对接结果能量均低于-7 kcal/mol。结论:结合已有文献报道,酸枣仁汤抗抑郁作用具有多成分、多途径、多靶点特点,通过影响PI3K-Akt、cAMP、TNF等多条信号通路,从抑制神经细胞凋亡、促进神经元的神经发生和增殖、抗神经炎症方面发挥抗抑郁作用,体现了中医整体观优越性,为后续酸枣仁汤治疗抑郁症的基础和临床进一步研究提供了思路和借鉴。

Objective:To investigate the main antidepressant mechanism of Suanzaoren Decoction based on network pharmacology and molecular docking.Method:The targets of the active components in Suanzaoren Decoction were searched through the TCM Systematic Pharmacology Database and Analysis Platform(TCMSP).Depression-related targets were retrieved through the Drugbank,GeneCards and OMIM databases,and the intersection of component targets and disease targets was obtained,thus constructing the protein-protein interaction(PPI)network between the component targets and depression targets of Suanzaoren Decoction by the STRING database.GO and KEGG enrichment analysis were conducted by the Metascape database.Molecular docking studies were conducted by the AutoDock 4.2 software.Result:90 active components were screened according to the pharmacokinetic parameters OB,BBB and DL,among which the main active components were(S)-Coclaurine,7-Methoxy-2-methyl isoflavone,Formononetin,Licochalcone A,Anhydroicaritin,Hederagenin,Myricanone,etc.63 intersection targets of component targets and disease targets were obtained,and the key targets were AKT1,NOS3,PTGS2,MAPK1,CHRM2,etc.The mechanism of drugs was related to PI3K-Akt,cAMP,TNF and other signaling pathways.The molecular docking technique validation showed that the energies of the molecular docking between the main active components in Suanzaoren Decoction and the key targets were all lower than-7 kcal/mol.Conclusion:Combined with previous reports,the antidepressant effect of Suanzaoren Decoction has multi-component,multi-pathway and multi-target characteristics,which exerts antidepressant effects in terms of inhibiting neuronal apoptosis,promoting neurogenesis and proliferation of neurons,and anti-neuroinflammation via affecting the PI3K-Akt,cAMP,TNF and other signaling pathways.It embodies the superiority of the holism of traditional Chinese medicine,and provides ideas and references for further basic and clinical research on the antidepressant effect of Suanzaoren Decoction.