基于网络药理学和实验验证分析丹皮酚治疗经前烦躁障碍症的作用机制

Mechanism of Action of Paeonol in the Treatment of Premenstrual Dysphoric Disorder Based on Network Pharmacology and Experimental Verification

关键词:  丹皮酚  经前烦躁障碍症  网络药理学  分子对接

Key words:  paeonol  premenstrual dysphoric disorder  network pharmacology  molecular docking

摘要:

目的 通过网络药理学和整体动物实验分析丹皮酚治疗经前烦躁障碍症(premenstrual dysphoric disorder，PMDD)的靶点及相关通路。方法 通过Swiss Target Prediction数据库获取丹皮酚作用靶点；通过OMIM、Drug Bank、Gene Cards、DisGeNET数据库获取PMDD发病机制靶点；使用STRING数据库对丹皮酚-PMDD交集靶点进行蛋白质-蛋白质相互作用网络分析；使用DAVID网站对交集靶点进行基因本体(GO)、京都基因与基因组百科全书(KEGG)富集分析；并对核心靶点进行分子对接验证。复制PMDD大鼠模型，检测海马脑区5-HT1A、MAOA、MAOB的mRNA的表达水平及5-HT水平，验证丹皮酚治疗PMDD的作用通路及靶点。结果 网络药理学发现丹皮酚与PMDD交集靶点16个，主要涉及5-HT信号通路的基因如5-HT1A、MAOA、MAOB等；整体动物实验发现丹皮酚可以提高模型大鼠5-HT1A、MAOA、MAOB的mRNA的表达水平，降低海马脑区5-HT水平。结论 本研究利用网络药理学成功预测了丹皮酚治疗PMDD作用靶点，结合整体动物试验证实丹皮酚治疗PMDD的作用机制与促进5-HT分解及提高5-HT1A表达相关，为丹皮酚临床治疗PMDD的机制研究提供理论和实验依据。

Abstract:

OBJECTIVE To analyze the targets and related pathways of paeonol in the treatment of premenstrual dysphoric disorder(PMDD) by network pharmacology and whole animal experiments. METHODS The action targets of paeonol were obtained from the SwissTargetPrediction database; the pathogenesis targets of PMDD were obtained from the OMIM, Drug Bank, Gene Cards and DisGeNET databases; the protein-protein interaction network analysis of the paeonol-PMDD intersection targets was performed by using the STRING database; Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis for intersection targets using DAVID website; and molecular docking verification for core targets. The PMDD rat model was replicated, and the mRNA expression levels of 5-HT1A, MAOA, and MAOB in the hippocampus as well as 5-HT levels were detected, the action pathways and targets of paeonol in the treatment of PMDD were verified. RESULTS Network pharmacology found that paeonol and PMDD had 16 intersection targets, mainly involving genes in the 5-HT signaling pathway, such as 5-HT1A, MAOA, MAOB, etc; the overall animal test found that paeonol could increase the mRNA expression levels of 5-HT1A, MAOA and MAOB decreased the level of 5-HT in the hippocampus. CONCLUSION In this study, network pharmacology is used to successfully predict the target of paeonol in the treatment of PMDD. Combined with the overall animal experiment, it is confirmed that the mechanism of paeonol in the treatment of PMDD is related to the promotion of 5-HT decomposition and the increase of 5-HT1A expression, which provide theoretical and experimental basis for the mechanism study of paeonol in clinical treatment of PMDD.