基于网络药理学的栀子豉汤抗抑郁作用机制研究

目的建立活性成分-作用靶点、蛋白相互作用、靶点相应的生物功能和通路网络,探讨栀子豉汤的抗抑郁作用机制。方法通过中药系统药理学技术平台(TCMSP)数据库并结合文献挖掘和整理获取栀子豉汤的主要活性成分。依据反向药效团匹配(Pharm Mapper)方法预测栀子豉汤活性成分的作用靶点。采用Cytoscape软件构建栀子豉汤活性成分-作用靶点网络。通过String数据库结合Cytoscape软件绘制蛋白相互作用网络,并用Systems dock Web Site对其进行验证。通过ClueGO结合Clue Pedia插件对其靶点生物功能及涉及的通路进行分析。结果栀子豉汤中筛选得到16个活性成分,涉及43个靶点,网络分析结果表明靶点主要参与细胞、组织、器官、代谢、免疫和对应激的应答等过程,通过调节瘦素、雌激素、丝裂原活化蛋白激酶级联(MAPK cascade)、脑源性神经营养因子-酪氨酸激酶受体(BDNF-Trk B)、5-羟色胺受体(5-HT receptor)、白细胞介素(IL)等信号通路来发挥抗抑郁作用。结论体现了中药多成分-多靶点-多通路的特点,为进一步开展栀子豉汤的抗抑郁作用机制研究提供了新思路和新方法。

Study on mechanism of antidepression of Zhizi Chi Decoction based on network pharmacology

Objective To explore the mechanism of antidepressant of Zhizi Chi Decoction by establishing active ingredients-targets, proteins interactions, biological functions and pathways of targets networks. Methods Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and Analysis Platform database combined with literatures mining were used to obtain the main active ingredients of Zhizi Chi Decoction. The targets of active ingredients of Zhizi Chi Decoction were predicted based on the PharmMapper method. Cytoscape software was applied to construct the active ingredients-targets network. Through the String database combined with Cytoscape software to draw the proteins interactions network, and use the Systems dock Web Site to verify part of its targets. The biological functions and related pathways were analyzed by ClueGO and CluePedia plugin. Results A total of 16 active ingredients and 43 targets were screened in Zhizi Chi Decoction. The results of network analysis showed that the targets involved in cells, tissues, organs, metabolism, immune, response to stress and other processes, and played an antidepressant role by regulating leptin, estrogen, MAPK cascade, BDNF-TrkB, 5-HT receptor and IL signal pathways. Conclusion This study reflects the characteristics of multi-components, multi-targets, and multi-pathways of traditional Chinese medicine, which provides new ideas and clues for further research on the antidepressant mechanism of Zhizi Chi Decoction.