基于网络药理学探索当归-黄芪-甘草治疗糖尿病足的作用机制

Exploration on the mechanism of Danggui-Huangqi-Gancao in the treatment of diabetic foot based on network pharmacology

目的:借助网络药理学理论探索当归-黄芪-甘草治疗糖尿病足(Diabetic Foot,DF)的作用机制。方法:运用多个数据库[中药系统药理学数据库与分析平台(TCMSP)、Uniprot、Gene Cards、Dis Ge NET、OMIM、TTD和STRING]和软件(“Venn”、Cytoscape 3.8.0和Cluster Profiler R)对数据挖掘得出的草药组合开展网络药理学研究。结果:共获得94个活性成分,对应238个作用靶点,确定槲皮素、山柰酚、芒柄花素和异鼠李素为关键活性成分。查询到1540个DF的关联基因,重叠基因112个,其中肿瘤坏死因子(Tumor Necrosis Factor,TNF)、丝氨酸/苏氨酸蛋白激酶1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、信号转导和转录激活因子3(Signal Transducers and Activators of Transcription 3,STAT3)、肿瘤蛋白p53(Tumor Protein p53,TP53)等25个基因被确定为关键基因。关键基因本体论(GO)富集到961条生物过程,与细胞氧化应激反应、化学应激反应和抗氧化反应等过程有关;11个细胞结构,主要是膜筏、膜微结构域和囊腔等细胞结构;29条分子功能,涉及细胞因子受体结合、磷酸酶结合、RNA聚合酶Ⅱ特异性DNA转录因子结合等功能。京都基因与基因组百科全书(KEGG)通路富集分析富集到120条通路,主要集中在脂质和动脉粥样硬化、人巨细胞病毒感染和TNF信号通路等通路中。结论:明确了当归-黄芪-甘草治疗DF的关键成分和关键靶点,揭示了关键靶点的作用机制,为后期研究提供依据。

Objective:To explore the mechanism of Danggui(Angelica)-Huangqi(Astragalus)-Gancao(Licorice)in the treatment of DF with the help of network pharmacological theory.Methods:Multiple databases(TCMSP,Uniprot,GeneCards,DisGeNET,OMIM,TTD and STRING)and software(Venn,Cytoscape 3.8.0 and ClusterProfiler R)were used to conduct network pharmacological studies on TCM medicine combinations derived from data mining.Results:A total of 94 active ingredients were obtained,corresponding to 238 target sites.Quercetin,kaempferol,onononetin and isorhamnetin were identified as the key active ingredients.There were 1540 DF associated genes,112 overlapping genes,and 25 genes such as TNF,AKT1,IL-6,STAT3 and TP53 were identified as key genes.GO obtained 961 biological processes,which were related to cellular oxidative stress,chemical stress and antioxidant response.There were 11 cellular components,which were mainly cell structures such as membrane raft,membrane microdomain and capsule cavity.There were 29 molecular functions,which involved cytokine receptor binding,phosphatase binding,RNA polymerase II specific DNA transcription factor binding,etc.KEGG analysis obtained 120 pathways,which were mainly in lipid and atherosclerosis,human cytomegalovirus infection and TNF signaling pathways.Conclusion:The key components and key targets of Danggui-Huangqi-Gancao in the treatment of DF are clarified,and the mechanism of action of the key targets is revealed,which provides the basis for the later study.