基于网络药理学的龟鹿二仙胶治疗创伤后应激障碍的作用机制研究

该文通过网络药理学的方法预测龟鹿二仙胶治疗创伤后应激障碍(PTSD)的多成分、多靶点、多途径的作用机制。基于TCMSP数据库、BATMAN-TCM数据库、化学专业数据库、DrugBank数据库获取龟鹿二仙胶的活性成分及对应靶点,从OMIM,TTD,DisGeNET数据库获取PTSD的已知治疗靶点,结合STRING数据库构建活性成分-疾病靶点蛋白互作网络,利用Cytoscape 3.6.0软件对该网络进行拓扑参数分析得到关键活性成分及其靶点。对关键靶点进行GO生物学过程分析和KEGG通路分析,通过Cytoscape 3.6.0软件构建龟鹿二仙胶"活性成分-靶点-通路"网络,采用SystemsDock在线分子对接工具进行对接验证。预测结果表明,龟鹿二仙胶共有67个活性成分和420个靶点,PTSD共有206个已知治疗靶点,Cytoscape 3.6.0拓扑参数分析后共有66个靶点,GO生物学过程分析得出58个条目,KEGG通路分析得出22条通路,分子对接结果显示,degree最大的靶点与其对应的活性成分、通路中疾病和药物的共同靶点与其对应的活性成分能有效结合。结果提示,龟鹿二仙胶可能通过调节突触可塑性、抗细胞凋亡、抗炎及促进恐惧记忆消退起到抗PTSD的作用,涉及的通路包括LTP信号通路、PI3K/Akt/mTOR信号通路、TNF信号通路、含血清素的神经突触通路以及多巴胺能神经突触通路等。该研究为进一步阐释龟鹿二仙胶治疗PTSD的药理机制提供了理论依据。

Study on mechanism of Guilu Erxianjiao in treatment of post-traumatic stress disorder based on network pharmacology

The aim of this paper was to predict the multi-compound, multi-target and multi-pathway mechanism of Guilu Erxianjiao in treating post-traumatic stress disorder(PTSD) based on network pharmacology. Active compounds and corresponding targets of Guilu Erxianjiao were obtained from TCMSP, BATMAN-TCM, Chemistry and DrugBank database, and known therapeutic targets of PTSD were obtained from OMIM, TTD and DisGeNET Database. The protein interaction network of compound-disease was then built by combining with the STRING Database. Topological parameters of the network were analyzed by Cytoscape 3.6.0 to get key active compounds and their targets. The GO biological process analysis and KEGG pathway analysis of the key targets were conducted. Based on the results of KEGG, the "compound-target-pathway" network was built by Cytoscape 3.6.0 and the results were verified by SystemsDock online molecular docking tool. The prediction results showed that there were 67 active compounds and 420 targets for Guilu Erxianjiao, and 206 known PTSD-related therapeutic targets. Besides, 66 targets, 58 terms and 22 pathways were obtained from Cytoscape 3.6.0 topological parameters analysis, GO biological process analysis, and KEGG pathway analysis, respectively. Molecular docking results showed that both target with the maximum degree value and common targets of PTSD and Guilu Erxianjiao in the pathway can be effectively combined with their corresponding active compounds through molecular docking. The results suggested that Guilu Erxianjiao could exert anti-PTSD effect by regulating synaptic plasticity, anti-apoptotic, anti-inflammatory and promoting fear memory extinction through pathways such as LTP, PI3 K/Akt/mTOR, TNF, serotonergic synapse and dopaminergic synapse. This study provides a theoretical basis for further elucidating pharmacological mechanisms of Guilu Erxianjiao in treating PTSD.