基于网络药理学研究补阳还五汤治疗高血压性脑出血的作用机制

Mechanism of action of Buyang Huanwu decoction in treatment of hypertensive cerebral hemorrhage:A study based on network pharmacology

目的:基于网络药理学探讨补阳还五汤治疗高血压性脑出血的作用机制。方法:通过TCMSP获取补阳还五汤中药的主要化学成分及活性物,利用UniProt数据库规范化合物作用的蛋白质靶点。通过Swiss ADME平台筛选潜在化学成分,将筛选后的化合物通过SwissTargetPrediction平台获取其靶点;通过GeneCards数据库获取疾病的主要靶点,利用Venny分析工具绘制Venny图,并得到两者交集靶点。利用STRING11.5及Cytoscape 3.9.1构建蛋白质-蛋白质相互作用(PPI)网络。利用Metascape数据平台对潜在靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果:获得药物活性成分黄芪17种、赤芍14种、川芎6种、当归2种、红花17种、桃仁19种,作用靶点646个,疾病靶点489个,药物-疾病交集靶点77个。关键基因主要为白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、血管内皮生长因子(VEGFA)、环加氧酶2(PTGS2)等。GO功能富集条目涉及炎症反应、对脂多糖的反应、膜筏、囊泡腔、抗氧化活性、激酶结合等。KEGG信号通路主要包括磷脂酰肌醇-3-激酶(PI3K-Akt)、白细胞介素-17(IL-17)等信号通路。结论:补阳还五汤治疗高血压性脑出血具有多成分、多靶点、多通路的特点,能起到抗炎、抗凋亡等作用,从而减少神经细胞凋亡,减轻脑水肿,改善神经功能损伤。

Objective:To investigate the mechanism of action of Buyang Huanwu decoction in the treatment of hypertensive cerebral hemorrhage based on network pharmacology.Methods:TCMSP was used to obtain the main chemical components and active substances of Buyang Huanwu decoction,and UniProt database was used to standardize the protein targets of compounds.Swiss ADME platform was used to screen for potential chemical components,and then SwissTargetPrediction platform was used to obtain their targets;GeneCards database was used to obtain the main targets of the disease,and Venny analytic tool was used to plot a Venn diagram and obtain the intersecting targets of the above two groups of targets.STRING11.5 and Cytoscape 3.9.1 were used to construct a protein-protein interaction network.Metascape data platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of potential targets.Results:The above analyses obtained 17 active components of Astragalus membranaceus,14 active components of Radix Paeoniae Rubra,6 active components of Rhizoma Chuanxiong,2 active components of Angelica sinensis,17 active components of Carthamus tinctorius,and 19 active components of peach seed,as well as 646 action targets,489 disease targets,and 77 drug-disease intersecting targets.Key genes mainly included IL-6,TNF,VEGFA,and PTGS2.GO terms mainly involved inflammatory response,response to lipopolysaccharide,membrane raft,vesicle cavity,antioxidant activities,and kinase binding,and KEGG signaling pathways mainly included PI3K-Akt and IL-17.Conclusion:Buyang Huanwu decoction has the features of multiple components,targets,and pathways in the treatment of hypertensive cerebral hemorrhage and can exert anti-inflammatory and anti-apoptosis effects to reduce neural cell apoptosis,alleviate cerebral edema,and improve neurovascular injury.