基于网络药理学方法和分子对接技术探讨芍药甘草汤合桃红四物汤治疗糖尿病周围神经病变的作用机制  

Exploration of Mechanism of Shaoyao Gancao Decoction Plus Taohong Siwu Decoction in Treating Diabetic Peripheral Neuropathy Based on the Network Pharmacology and Molecular Docking Technology

作　　者：刘莹[1] 林旋[1,2] 张珏 姚南珍 赵一涵 LIU Ying;LIN Xuan;ZHANG Jue;YAO Nanzhen;ZHAO Yihan(The Eighth Clinical Medical School of Guangzhou University of Chinese Medicine,Foshan Guangdong 528000,China;The First People's Hospital of Foshan,Foshan Guangdong 5280o0,China;Foshan Hospital of Tradition Medicine,Foshan Guangdong528000,China)

机构地区：[1]广州中医药大学第八临床医学院,广东佛山528000 [2]佛山市第一人民医院,广东佛山528000 [3]佛山市中医院,广东佛山528000

出　　处：《新中医》2024年第8期30-40,共11页New Chinese Medicine

摘　　要：目的:运用网络药理学方法及分子对接技术探讨芍药甘草汤合桃红四物汤治疗糖尿病周围神经病变(DPN)的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)数据库筛选芍药甘草汤合桃红四物汤的活性成分及相关靶点信息;从DrugBank、PharmGKB、GeneCards、OMIM和TTD数据库中获取DPN的靶点基因。运用Cytoscape软件、STRING数据库构建芍药甘草汤合桃红四物汤活性成分-DPN共同靶点基因关系网络及共同靶点基因的蛋白质相互作用(PPI)网络。利用R语言软件进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。采用AutoDock Vina软件进行分子对接。结果:共获得161个芍药甘草汤合桃红四物汤活性成分,184个芍药甘草汤合桃红四物汤活性成分-DPN共同靶点基因。核心活性成分为槲皮素、木犀草素、山奈酚、柚皮素、7-甲氧基-2-甲基异黄酮,核心靶点基因为信号传导及转录激活蛋白3(STAT3)、丝裂原活化蛋白激酶3(MAPK3)、热休克蛋白90AA1(HSP90AA1)、丝裂原活化蛋白激酶1(MAPK1)、转录因子p65(RELA)。GO功能富集分析得到2940条GO条目,KEGG通路富集分析得到182条信号通路。分子对接结果显示,木犀草素与HSP90AA1的结合活性最好。结论:芍药甘草汤合桃红四物汤具有多成分、多靶点、多通路的效应特点,其作用机制可能是槲皮素、木犀草素、山奈酚、柚皮素、7-甲氧基-2-甲基异黄酮等活性成分作用于STAT3、MAPK3、HSP90AA1、MAPK1、RELA等靶点基因,调控磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)、白细胞介素-17(IL-17)、肿瘤坏死因子(TNF)、缺氧诱导因子1(HIF-1)等多条信号通路,通过抗氧化应激、抑制炎症反应、保护神经细胞、改善胰岛素抵抗发挥治疗DPN的作用。Objective:To explore the mechanism of Shaoyao Gancao Decoction plus Taohong Siwu Decoction in the treatment of diabetic peripheral neuropathy(DPN)based on network pharmacology and molecular docking technology.Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was searched for the active ingredients and related target proteins of Shaoyao Gancao Decoction plus Taohong Siwu Decoction.The target genes of DPN were obtained from DrugBank,PharmGKB,GeneCards,OMIM,and TTD databases.Cytoscape software and STRING database were used to construct the relationship network of the active ingredients-DPN common target genes and the protein-protein interaction(PPI)network of common target genes.The enrichment analysis of Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway were performed using R language software.AutoDock Vina software was used for molecular docking.Results:A total of 161 active ingredients and 184 active ingredient-DPN common target genes were obtained from Shaoyao Gancao Decoction plus Taohong Siwu Decoction.The core active ingredients were quercetin,luteolin,kaempferol,naringenin,7-methoxy-2-methylisoflavones,and the core target genes were signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase 3(MAPK3),heat shock protein 90AA1(HSP90AA1),mitogen-activated protein kinase 1(MAPK1),and nuclear factor-κB(RELA).The results of GO functional enrichment analysis showed 2940 GO entries and KEGG pathway enrichment analysis showed 182 signaling pathways.The molecular docking results showed that luteolin had the best binding activity with HSP90AA1.Conclusion:Shaoyao Gancao Decoction plus Taohong Siwu Decoction has the characteristics of multi-ingredients,multi-targets and multi-pathways.Its potential mechanism may be that active ingredients such as quercetin,luteolin,kaempferol,naringenin,and 7-methoxy-2-methylisoflavones act on STAT3,MAPK3,HSP90AA1,MAPK1,RELA,and other target genes,and regulate multiple signal

关 键 词：糖尿病周围神经病变 网络药理学 分子对接 芍药甘草汤 桃红四物汤 

分 类 号：R285[医药卫生—中药学] R587.2[医药卫生—中医学]