基于UPLC-Q-Exactive Orbitrap-MS技术及网络药理学探讨化浊散结除痹方治疗痛风性关节炎的药效物质及潜在机制  

Exploration of pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in treatment of gouty arthritis based on UPLC-Q-Exactive Orbitrap-MS technology and network pharmacology

作　　者：肖艳 张婷 张英杰[2,3] 黄彬 陈鹏[2,3] 陈小华 黄鸣清 陈雪婷[6] 苏友新 郭洁梅[3] XIAO Yan;ZHANG Ting;ZHANG Ying-jie;HUANG Bin;CHEN Peng;CHEN Xiao-hua;HUANG Ming-qing;CHEN Xue-ting;SU You-xin;GUO Jie-mei(College of Rehabilitation Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Traditional Chinese Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Key Laboratory of Orthopedics&Traumatology of Traditional Chinese Medicine and Rehabilitation,Ministry of Education,Fuzhou 350122,China;Academy of Intergrative Medicine,College of Intergrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;First Clinical Medicine College,Fujian University of Traditional Chinese Medicine,Fuzhou 350004,China;College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学康复医学院,福建福州350122 [2]福建中医药大学中医学院,福建福州350122 [3]中医骨伤及运动康复教育部重点实验室,福建福州350122 [4]福建中医药大学中西医结合学院中西医结合研究院,福建福州350122 [5]福建中医药大学第一临床医学院,福建福州350004 [6]福建中医药大学药学院,福建福州350122

出　　处：《中国中药杂志》2025年第2期444-464,共21页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划“中医药现代化”重点专项(2022YFC3501200,2022YFC3501205);国家自然科学基金项目(82474326);国家中医药管理局2021年岐黄学者支持项目(国中医药人教函[2022]No.6);福建省教育厅、福建省工信厅2023年技术创新重点攻关及产业化项目(2023XQ013);福建省省级财政专项(X2022008-财政专项)。

摘　　要：基于超高效液相色谱-四极杆静电场轨道阱质谱(UPLC-Q-Exactive Orbitrap-MS)技术及网络药理学探讨化浊散结除痹方治疗痛风性关节炎(gouty arthritis,GA)的药效物质及潜在机制。采用UPLC-Q-Exactive Orbitrap-MS技术鉴定化浊散结除痹方药物成分,对其有效成分进行定性分析,共鉴定出化浊散结除痹方中184个有效成分;通过PharmMapper在线数据库筛选有效成分靶点897个,在OMIM、GeneCards、CTD等数据库获取GA相关的疾病靶点491个,进行韦恩分析后获得二者的交集靶点60个,通过Cytoscape平台构建“成分靶点-GA靶点”网络图,利用STRING数据库构建蛋白-蛋白互作网络,筛选出16个核心靶点,将核心靶点进行基因本体论(Gene Ontology,GO)与京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路的富集分析,并构建“成分-靶点-通路”网络图,发现该方治疗GA的主要有效成分为酚类、黄酮类、生物碱类、萜类化合物,关键靶点有SRC、MMP3、MMP9、REN、ALB、IGF1R、PPARG、MAPK1、HPRT1、CASP1,通过GO分析发现其治疗GA主要涉及脂质反应、细菌反应、生物刺激的反应等生物过程,通过KEGG分析发现其治疗GA相关的通路有脂质和动脉粥样硬化、中性粒细胞胞外诱捕网、IL-17等。综上,该研究揭示了酚类、黄酮类、生物碱类、萜类化合物可能是化浊散结除痹方治疗GA的核心药效物质,其药效机制可能与SRC、MMP3、MMP9等靶点及脂质和动脉粥样硬化、中性粒细胞胞外诱捕网、IL-17等通路相关。Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-QExactive Orbitrap-MS)technology and network pharmacology,this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA).UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction,and the qualitative analysis of its active ingredients was carried out,with a total of 184 active ingredients identified.A total of 897 active ingredient targets were screened through the PharmMapper database,and 491 GA-related disease targets were obtained from the OMIM,GeneCards,CTD databases.After Venn analysis,60 intersecting targets were obtained.The component target-GA target network was constructed through the Cytoscape platform,and the STRING database was used to construct a protein-protein interaction network,with 16 core targets screened.The core targets were subjected to Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses,and the component-target-pathway network was constructed.It was found that the main active ingredients of the formula for the treatment of GA were phenols,flavonoids,alkaloids,and terpenoids,and the key targets were SRC,MMP3,MMP9,REN,ALB,IGF1R,PPARG,MAPK1,HPRT1,and CASP1.Through GO analysis,it was found that the treatment of GA mainly involved biological processes such as lipid response,bacterial response,and biostimulus response.KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis,neutrophil extracellular traps(NETs),IL-17,and so on.In summary,phenols,flavonoids,alkaloids,and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA,and the pharmacodynamic mechanism may be related to SRC,MMP3,MMP9,and other targets,as well as lipids and atherosclerosis,NETs,IL-17,and other pathways.

关 键 词：化浊散结除痹方 痛风性关节炎 超高效液相色谱-四极杆静电场轨道阱质谱 网络药理学 药效物质 机制 

分 类 号：R285[医药卫生—中药学]