基于网络药理学探析四君子汤抗衰老作用机制

Study on the Anti-aging Mechanism of Sijunzi Decoction(四君子汤)Based on Network Pharmacology

目的借助网络药理学方法初步探究四君子汤抗衰老的作用机制。方法基于中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选四君子汤中4味中药的主要活性成分及靶点,分别在Genecards和人类孟德尔遗传在线(online mendelian inheritance in man,OMIM)疾病数据库中检索衰老相关靶点,用Cytoscape3.7.0软件对四君子汤活性成分靶点以及抗衰老靶点进行可视化。在STRING在线平台构建共表达靶点蛋白质-蛋白质互作网络,通过R3.6.2软件对四君子汤抗衰老靶基因进行基因本体(Gene Ontology,GO)功能分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果 TCMSP中筛选出71个主要成分,210个成分靶点。疾病数据库获取到279个衰老靶点。通过靶点映射发现四君子汤活性成分作用的丝氨酸/苏氨酸蛋白激酶(AKT1)、血管内皮生长因子A(VEGFA)、胱天蛋白酶3(CASP3)、白细胞介素6(IL-6)、表皮生长因子(EGF)等55个共表达靶基因,发现靶基因主要参与细胞因子受体结合、细胞因子活性、受体配体活性等生物过程,主要富集在糖尿病并发症(AGE-RAGE)、磷脂酰肌醇3’-激酶-Akt(PI3K-Akt)、缺氧诱导因子1(hypoxia-inducible factor 1,HIF-1)、白介素17(interleukin17,IL-17)及肿瘤坏死因子(tumor necrosis factor,TNF)等信号通路和多种癌症途径。结论本研究初步探究了四君子汤抗衰老作用的活性成分及靶基因,网络关系构建及通路富集结果充分体现了其多成分-多靶点-多途径的复杂特点,为进一步深入阐释其抗衰老机制奠定了基础。

Objective With the help of the network pharmacology method to explore the anti-aging mechanism of Sijunzi Decoction(四君子汤). Methods The main active components and targets of Sijunzi Decoction were selected based on the network pharmacology database and analysis platform(TCMSP),and the aging related targets were searched in the genecards and OMIM disease database respectively. The active components and anti-aging targets of Sijunzi Decoction were visualized with the software of Cytoscape3.7.0. The coexpression target protein protein interaction network was constructed on the string online platform to display the core target gene with the degree value. The GO function analysis and KEGG pathway enrichment of the target gene of Sijunzi Decoction for anti-aging were carried out by using the R3.6.2 software. Results 71 main components and 210 component targets were selected from TCMSP. 279 aging targets were obtained from the disease database. Through target mapping,55 coexpressed target genes,such as AKT1,VEGFA,CASP3,IL-6 and EGF,were found to be involved in the biological processes of cytokine receptor binding,cytokine activity and receptor ligand activity,which are mainly enriched It can be found in AGERAGE signaling pathway in diabetic complications,PI3 K-Akt,HIF-1,IL-17,TNF signaling pathway and many cancer pathways. Conclusion This study preliminarily explored the active ingredients and target genes of Sijunzi Decoction in anti-aging effect. The results of network relationship construction and pathway enrichment fully reflected the complex characteristics of its multi-component,multi-target and multichannel,which laid a foundation for further explanation of its anti-aging mechanism.