目的 利用网络药理学方法及分子对接技术,分析四逆散治疗青少年抑郁症的潜在作用机制,并进行实验验证相关结果。方法 通过TCMSP、ETCM数据库筛选出四逆散(柴胡、枳实、白芍、甘草)的有效化学成分及作用靶点,在GeneCards与OMIM数据库中筛选青少年抑郁症的主要靶点,结合韦恩图得到药物与疾病的共同靶点。利用Cytoscape 3.9.1软件绘制四逆散的中药-活性成分-靶点作用网络；使用STRING平台构建药物-疾病-共同靶点的蛋白质互作网络图(portein-protein interaction network, PPI),筛选后得到核心作用靶点；利用Metascape平台对核心靶点进行富集分析；通过软件AutoDockTools 1.5.7进行分子对接评估有效活性成分与潜在核心靶点的结合能力；通过蛋白免疫印迹(western blot,WB)实验验证四逆散抗青少期抑郁的潜在靶点。结果 本研究筛选出四逆散治疗青少年抑郁症的核心有效活性成分包括有槲皮素、山奈酚、异鼠李素、芍药苷等,通过PPI网络拓扑分析,确定了潜在核心靶点包括AKT1、IL6、PPARG、PTGS2、F7等。分子对接结果表明活性物质与其主要靶点结合活性较强。WB实验验证了AKT1、IL1B、IL6是四逆散抗青少期抑郁相关的潜在靶点。PPI网络四逆散治疗青少年抑郁的主要生物过程有对激素的反应等,调节的主要信号通路包括AGE-RAGE、PI3K-AKT等。结论 本研究初步确认了四逆散抗青少年抑郁症的有效活性成分及靶点信息,揭示了四逆散治疗青少年抑郁症的潜在作用机制。

Objective Network pharmacology and molecular docking technology were used to analyze the potential mechanism of Sinisan (SNS) in the treatment of adolescent depression, and the relevant results were verified by experiments. Methods Through the TCMSP and ETCM databases, the effective chemical components and targets of SNS (Chaihu, Zhishi, Baishao and Gancao) were screened, and the main targets of adolescent depression were screened in the GeneCards and OMIM databases, and the common targets of drugs and disease were obtained by Venn diagram. Cytoscape 3.9.1 software was used to draw the Chinese herb-active ingredient-target action network of SNS. The STRING platform was used to construct a portein-protein interaction network (PPI) of drug-disease-common targets, and the core targets were obtained after screening. The Metascape platform was used to perform enrichment analysis of core targets. Molecular docking was carried out through the software AutoDockTools 1.5.7 to evaluate the binding ability of effective active ingredients to potential core targets. Western blotting (WB) experiments were used to verify the potential targets of SNS against adolescent depression. Results The core effective active ingredients of SNS in the treatment of adolescent depression include quercetin, kaempferol, isorhamnetin, paeoniflorin, etc., and the potential core targets including AKT1, IL6, PPARG, PTGS2, F7, etc., were identified through PPI network topology analysis. The molecular docking results showed that the active substance had strong binding activity to its main target. WB experiments verified that AKT1, IL1B and IL6 were potential targets related to anti-adolescent depression. The main biological processes of PPI network four inverse dispersion in the treatment of adolescent depression include hormone response, and the main signaling pathways regulated such as AGE-RAGE and PI3K-AKT signaling pathway. Conclusion This study preliminarily confirmed the effective active ingredients and target information of SNS treatment in adolescent depression, and revealed the potential mechanism of SNS in the treatment of adolescent depression.

国家自然科学基金项目（青年项目）