基于系统药理学和文献收集的滋肾平颤方加减治疗帕金森病伴抑郁机制探讨研究

Study on the Mechanism of Modified Zishen Pingchan Formula in the Treatment of Depression in Parkinson’s Disease Based on Systemic Pharmacology and Literature Collection

目的:基于系统药理学和相关研究文献分析预测滋肾平颤方加减治疗帕金森病伴抑郁(DPD)的主要活性成份、潜在作用靶点及分子作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)、TCM@TAIWAN台湾中医药资料库、PubChem、Swiss ADME、Swiss Target Prediction平台筛选滋肾平颤方加减中的主要化学成份及其作用靶点,利用GeneCards和DisGeNET数据库筛选DPD的相关靶点,采用STRING和Cytoscape软件构建共同靶点蛋白相互作用(PPI)网络及中药-活性成份网络图。通过DAVID数据库对关键靶点进行GO功能富集和KEGG通路富集分析,同时查阅滋肾平颤方相关研究文献并进行归纳、整理和分析。结果:共筛选出滋肾平颤方加减主要活性成份82个,作用靶点143个,其中36个是与DPD共有的核心靶点。GO功能富集分析显示生物过程主要包括RNA聚合酶II启动子转录的正调控、对药物的反应和蛋白质自磷酸化;细胞组分主要有质膜、质膜的组成部分以及细胞膜;分子功能涵盖了蛋白质结合、ATP结合以及可识别蛋白结合等。KEGG通路富集分析揭示滋肾平颤方加减中生物活性化合物主要通过神经活性配体-受体相互作用、Rap1、cAMP等信号通路发挥抗DPD的作用。结论:通过系统药理学结合文献收集分析,滋肾平颤方加减可能通过槲皮素、山奈酚和去氢骆驼蓬碱等关键成份,作用于AKT1、EGFR和DRD2等核心靶点,通过神经活性配体-受体相互作用、Rap1和cAMP等信号通路发挥治疗DPD的作用。

Objective:To analyze and predict the main active components,potential targets and molecular mechanisms of Modified Zishen Pingchan(MZSPC)formula in the treatment of depression in Parkinson’s disease(DPD)based on the systemic pharmacology and related literature.Methods:The main active components and their action targets of MZSPC formula were screened by TCMSP,TCM@TAIWAN,PubChem,Swiss ADME,and Swiss Target Prediction platforms.The GeneCards and DisGeNET databases were used to screen the related targets of DPD,and STRING and Cytoscape software were used to construct protein-protein interaction(PPI)and herb-ingredient networks.Gene ontology(GO)function enrichment and KEGG pathway enrichment analyses were performed on the core targets through DAVID database.Then the related research literature of MZSPC formula was reviewed,summarized,sorted and analyzed.Results:A total of 82 main active ingredients and 143 targets were screened,among which 36 were common core targets related with DPD.GO functional enrichment analysis showed that biological processes mainly included positive regulation of transcription from RNA polymerase Ⅱ promoter,response to drug,and protein autophosphorylation;cellular components mainly included plasma membrane,integral component of plasma membrane and membrane;molecular functions covered protein binding,ATP binding,and identical protein binding.KEGG pathway enrichment analysis revealed that the bioactive compounds in MZSPC formula mainly exerted their anti-DPD effects through Neuroactive ligand-receptor interaction,Rap1 and cAMP signaling pathways.Conclusion:Through systematic pharmacology combined with literature collection and analysis,the MZSPC formula might act on core targets such as AKT1,EGFR,and DRD2 through key components such as quercetin,kaempferol,and harmine.Through neuroactive ligand-receptor interaction,Rap1,cAMP and other signaling pathways played roles in the treatment of DPD.