经典名方人参五味子汤治疗脾肺气虚证的药效物质基础和作用机制分析  

Analysis on Pharmacodynamic Material Basis and Mechanism of Famous Classical Formula Renshen Wuweizi Tang in Treatment of Spleen and Lung Qi Deficiency Syndrome

作　　者：李珊珊 钟余特 向小梅 康伟 周书繁 王萍[1] 许海玉[1] LI Shanshan;ZHONG Yute;XIANG Xiaomei;KANG Wei;ZHOU Shufan;WANG Ping;XU Haiyu(Key Laboratory for Research and Evaluation of Traditional Chinese Medicine,National Medical Products Administration,Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Liaoning Herbapex Pharmaceutical(Group)Co.Ltd.,Benxi 117000,China)

机构地区：[1]中国中医科学院中药研究所,国家药品监督管理局中医药研究与评价重点实验室,北京100700 [2]辽宁上药好护士药业(集团)有限公司,辽宁本溪117000

出　　处：《中国实验方剂学杂志》2025年第8期31-39,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划项目(2023YFC2308204);中国中医科学院科技创新工程项目(CI2023C013YL);中国中医科学院使命导向改革重点专项(CI2023E001TS01)。

摘　　要：目的:基于超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS)、网络药理学及分子对接技术,挖掘经典名方人参五味子汤治疗脾肺气虚证的药效物质基础和作用机制。方法:采用UPLC-Q-TOF-MS/MS系统表征与鉴定人参五味子汤水煎液中的化学成分。运用网络药理学方法进行潜在活性成分筛选,收集成分靶标与脾肺气虚证相关证候基因集,通过STRING数据库获取蛋白质相互作用关系。使用Cytoscape 3.9.1构建“方-证”关联网络并计算拓扑特征值,对核心基因进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析以探索潜在药效环节,计算方药靶标网络到药效环节基因网络之间的平均最短路径以发现优势药效环节,使用MCODE插件从优势药效环节中辨识出核心基因簇,通过基因表达综合数据库(GEO)对其进行验证,并对关键成分与核心靶点进行分子对接。结果:在负离子模式下鉴定了137个成分,正离子模式下鉴定了80个成分,去重后共有185个成分,主要由三萜皂苷类(49个)和黄酮类(54个)化合物组成。基于“方-证”关联网络分析,确定“能量代谢”是人参五味子汤治疗脾肺气虚证的优势药效环节;分子对接结果显示,源于该方剂中人参、白术、甘草、茯苓4味药材的腺苷、白术内酯Ⅱ、白术内酯Ⅲ、人参皂苷Rg1、甘草皂苷B2、甘草皂苷E2、菜油甾醇7个成分可能通过作用于肿瘤坏死因子(TNF)、甘油醛-3-磷酸脱氢酶(GAPDH)、环磷腺苷效应元件结合蛋白1(CREB1)、白细胞介素(IL)-6、过氧化物酶体增殖物激活受体α(PPARα)、核转录因子-κB1(NF-κB1)6个靶标发挥对能量代谢的调控作用,从而改善脾肺气虚证相关疾病症状。结论:该研究建立了快速表征和鉴定人参五味子汤水煎液中化学成分的液质联用分析方法,拓展了对该方的物质组成的认识,并发现7个成分可能通过6个靶标作用�Objective:Based on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS),network pharmacology and molecular docking techniques,to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome.Methods:The chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS,and network pharmacology was used to screen potential active ingredients,collect component targets and gene sets related to spleen-lung Qi deficiency syndrome,and obtain protein interaction relationships through STRING.Cytoscape 3.9.1 was used to construct a"formula-syndrome"association network and calculate topological feature values.Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links,the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links,and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links,which were validated using Gene Expression Omnibus(GEO),and molecular docking was performed between key components and core targets.Results:One hundred and thirty-seven components were identified in the negative ion mode,and eighty components were identified in the positive ion mode.After deduplication,a total of 185 components were identified,mainly composed of triterpenoid saponins(49)and flavonoids(54).Based on the"formula-syndrome"correlation network analysis,energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome.The results of molecular docking showed that 7 components(adenosine,atractylenolideⅡ,atractylenolideⅢ,ginsenoside Rg1,glycyrrhizin B2,glycyrrhizin E2 and campesterol)from 4 medicinal materials(Gin

关 键 词：人参五味子汤 经典名方 超高效液相色谱-四极杆-飞行时间串联质谱法(UPLC-Q-TOF-MS/MS) 网络药理学 分子对接 药效物质 作用机制 

分 类 号：R277[医药卫生—中医学] R256[理学—分析化学] O657[理学—化学]