基于网络药理学探究肉桂治疗慢性肾脏病的作用机制

Mechanism of Rougui(Cinnamomum Cassia Presl)in Treating Chronic Kidney Disease Based on Network Pharmacology

目的:采用网络药理学方法建立“药效成分-疾病靶标-生物学通路”之间的关系,筛选肉桂治疗慢性肾脏病的作用靶点,明确其作用机制。方法:采用中药系统药理学成分分析平台(BATMAN-TCM)数据库获得肉桂的活性化合物,利用PubChem数据库,获取化合物的SMILES结构,将SMILES结构导入SwissTargetPrediction平台,预测活性成分的潜在靶点,再通过GeneCards数据库获得相关化合物靶点,取两者交集得到肉桂作用靶点。通过TTD、DrugBank、OMIM、GAD、DisGeNET数据库获得CKD疾病相关靶点,并与肉桂作用靶点取交集。利用STRING数据库及Cytoscape3.2.1软件构建靶点相互作用网络图,并利用cytoHubba插件的MCC算法筛选关键靶点;基于DAVID数据库对靶点进行GO富集和KEGG富集分析。结果:共得到肉桂活性化合物18个,肉桂-CKD交集靶点29个。经过MCC算法筛选得到关键基因10个,包括雌激素受体alpha、人环加氧酶1、表皮生长因子受体、血管内皮生长因子受体、基质金属蛋白酶9、基质金属蛋白酶2、成纤维细胞生长因子受体1、丝氨酸蛋白酶抑制剂-1、DNA多聚酶B、多药耐药性蛋白1、B细胞淋巴瘤/白血病-2。GO富集共118个结果,主要包括细胞对缺氧的反应、丝裂原活化蛋白激酶活性的正调节、血管生成的正调节、炎症反应、磷脂酶C活性的正调节、蛋白自体磷酸化、对白细胞介素-1的细胞反应、血管内皮生长因子受体信号通路的正调节等。KEGG富集相关通路共51条,包括NF-кB信号通路、PI3K-Akt信号通路、TNF信号通路、Ras信号通路、Rap1信号通路等。结论:通过网络药理学初步预测肉桂在慢性肾脏病治疗中改善糖脂代谢与胰岛素抵抗、抗氧化、抗炎与免疫调节、抗凝、促进成血管生成、改善组织局部血供等潜在作用机制,为下一步研究提供理论依据。

Objective:To establish the relationship between"pharmaceutical components-disease targets-biological pathways"by using network pharmacology methods,to screen the target of cinnamon treatment for chronic kidney disease,and to clarify its mechanism of action.Methods:Use the Chinese Medicine System Pharmacological Ingredient Analysis Platform(BATMAN-TCM)database to obtain the active compounds of Cinnamon.Use the PubChem database to obtain the SMILES structure of the compound.The database obtains the relevant compound targets,and takes the intersection of the two to obtain the cinnamon action target;obtains the CKD disease-related targets through the TTD,DrugBank,OMIM,GAD,and DisGeNET databases,and takes the intersection with the cinnamon action target;using the STRING database and Cytoscape3.2.1 The software constructs the target interaction net-work diagram,and uses the cytoHubba plug-in MCC algorithm to screen key targets;based on the DAVID database,GO enrichment and KEGG enrichment analysis are performed on the targets.Results:A total of 18 active compounds of cinnamon and 29 targets of cinnamon-CKD intersection were obtained.After screening by MCC algorithm,10 key genes were obtained,including ESR1,PTGS1,EGFR,KDR,MMP9,MMP2,FGFR1,SERPINE1,POLB,ABCB1 and BCL2.A total of 118 results were enriched by GO,mainly including the cellular response to hypoxia,the positive regulation of mitogen-activated protein kinase activity,the positive regulation of angiogenesis,the inflammatory response,the positive regulation of phospholipase C activity,protein autophosphorylation,cellular response to interleukin 1,positive regulation of vascular endothelial growth factor receptor signaling pathway.KEGG enriches a total of 51 related pathways,including NF-кB signaling pathway,PI3K-Akt signaling pathway,TNF signaling pathway,Ras signaling pathway,Rap1 signaling pathway,etc.Conclusion:Through network pharmacology,Cinnamon has been initially predicted to improve glucose and lipid metabolism and insulin resistance in the treatment of chronic kidney disease;antioxidant,antiinflammatory and immune regulation;anticoagulation,promote angiogenesis,and improve the local blood supply of tissues.Provide theoretical basis for the next research.