基于网络药理学熟地黄治疗帕金森病的作用机制研究

Action mechanism of Rehmannia glutinosa for treating Parkinson′s disease:a network pharmacology-based study

目的基于网络药理学探讨熟地黄治疗帕金森病的作用机制。方法在中药系统药理学数据库与分析平台筛选熟地黄的有效成分,通过UniProt数据库筛选中药作用靶点。在GeneCards数据库和OMIM数据库中检索帕金森病的疾病靶点。将帕金森病相关靶点和熟地黄作用靶点取交集,得到中药-疾病靶点,并绘制韦恩图。构建中药-成分-疾病-靶点调控网络,并建立中药-疾病靶点蛋白相互作用网络、筛选核心基因。对核心靶点进行生物功能和通路分析。结果共获得有效活性成分2个(β-谷甾醇和豆甾醇)和中药靶点26个。获得帕金森病相关靶点7058个,取交集后得到19个中药-疾病靶点。中药-有效成分-疾病-靶点调控网络显示熟地黄主要通过豆甾醇作用于19个帕金森病的疾病靶点。熟地黄治疗帕金森病的核心基因可能为MAOA、ADRA1B、ADRA1A、MAOB、SLC6A2等。核心靶点涉及65条生物过程,主要包括G蛋白偶联胺受体活性、肾上腺素能受体活性、儿茶酚胺结合、G蛋白偶联神经递质受体活性、神经递质受体活性、乙酰胆碱受体活性、G蛋白偶联、5-羟色胺受体活性等。核心靶点共涉及27条通路,主要包括神经活性配体-受体相互作用通路、钙信号通路、心肌细胞肾上腺素能信号转导通路、环磷酸鸟苷-蛋白激酶G信号通路、5-羟色胺能突触通路、环磷酸腺苷信号通路、多巴胺能突触通路、胆碱能突触通路等。结论熟地黄可能主要是通过豆甾醇作用于MAOA、ADRA1B、ADRA1A、MAOB、SLC6A2等靶点,从多个途径发挥治疗帕金森病的作用。

Objective To explore the action mechanism of Rehmannia glutinosa for treating Parkinson′s disease(PD)based on network pharmacology.Methods The active ingredients of Rehmannia glutinosa were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the action targets of Chinese medicine were screened in the UniProt database.Disease targets of PD were retrieved in the GeneCards database and OMIM database.Intersection between PD related targets and action targets of Rehmannia glutinosa was conducted,then Chinese medicine-disease targets were obtained and Venn diagram was drew.A regulatory network of Chinese medicine-ingredients-disease-targets was constructed;besides,a protein-protein interaction network of Chinese medicine-disease targets was established,and the core genes were screened.Biological function and pathway enrichment analysis was performed on the core targets.Results Two active ingredients(includingβ-sitosterol and stigmasterol)and 26 targets of Chinese medicine were obtained.Totally 7058 PD related targets were collected,and 19 Chinese medicine-disease targets were derived from the intersection.The regulatory network of Chinese medicine-active ingredient-disease-targets showed that Rehmannia glutinosa acted on 19 disease targets of PD mainly by stigmasterol.The core genes involving Rehmannia glutinosa treating PD might consist of MAOA,ADRA1B,ADRA1A,MAOB and SLC6A2,etc.The core targets involved 65 biological processes,mainly including G protein-coupled amine receptor activity,adrenergic receptor activity,catecholamine binding,G protein-coupled neurotransmitter receptor activity,neurotransmitter receptor activity,acetylcholine receptor activity,G protein coupling,and 5-hydroxytryptamine receptor activity.The core targets involved 27 pathways,mainly including neuroactive ligand-receptor interaction pathway,calcium signaling pathway,adrenergic signal transduction pathway in cardiomyocytes,cyclic guanosinc monophosphate-protein kinase G signaling pathway,serotonergic synapse signaling pathway,cyclic adenosine monophosphate signaling pathway,dopaminergic synapse signaling pathway,and cholinergic synapse signaling pathway.Conclusion Rehmannia glutinosa probably and mainly acts on the targets through stigmasterol,such as MAOA,ADRA1B,ADRA1A,MAOB and SLC6A2,thus exerting an therapeutic effect on PD by multiple pathways.