基于UPLC-Q-Orbitrap HRMS及GC-MS结合网络药理学和分子对接的彝药黑根抗类风湿性关节炎的药效物质研究  

Mechanism of action of Yi medicine Heigen(Inula nervosa(Wallich ex Candolle)Anderberg)in treatment of rheumatoid arthritis based on UPLC-Q-Orbitrap HRMS and GC-MS combined with network pharmacology and molecular docking

作　　者：赵倩[1] 樊锦雅 古锐[2] ZHAO Qian;FAN Jinya;GU Rui(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan;School of Ethnic Medicine,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]成都中医药大学民族医药学院,四川成都611137

出　　处：《中药与临床》2024年第3期52-60,共9页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家重点研发计划(2019YFC1712305);四川省药品监督管理局中药(民族药)标准提升项目(510201202102305)。

摘　　要：目的:探讨彝药黑根治疗类风湿性关节炎潜在的作用机制以及主要活性成分。方法:运用UPLC-Q-Orbitrap HRMS及GC-MS技术分析黑根的化学成分,利用Swiss Target进行活性成分的靶点筛选和预测,同时在Genecard、OMIM、Dis Ge NET等数据库中筛选类风湿性关节炎相关靶点,利用Cytoscape3.9.0软件构建“活性成分-靶点”网络模型,运用String数据分析平台进行蛋白互作网络分析,并且利用基因富集分析在线工具对核心靶点进行GO富集分析和KEGG通路分析,最后使用分子对接对网络药理学内容进行初步验证。结果:共鉴定出黑根化学成分78个,筛选后活性成分50个,237个潜在作用靶点与类风湿性关节炎相关,包括STAT3、AKT1、EGFR等关键靶点。通路富集分析PI3K-Akt通路、JAK-STAT等信号通路可能是黑根发挥抗类风湿性关节炎的主要途径。通过分子对接技术得出主要活性成分(异绿原酸B、异绿原酸C)与关键靶点有较好结合力。结论:研究初步表明黑根通过多成分、多靶点、多途径治疗类风湿性关节炎的作用,为后续黑根物质基础研究提供了理论依据。Objective:To investigate the potential mechanism of action and the main active ingredients of Yi medicine Heigen in the treatment of rheumatoid arthritis.Methods:The chemical composition of Heigen was analyzed by UPLC-Q-Orbitrap HRMS and GC-MS.The targets of active ingredients were screened and predicted by SwissTarget.The rheumatoid arthritis-related targets were screened in Genecard,OMIM,DisGeNET and other databases.The network model of"active ingredient-target"was constructed using Cytoscape 3.9.0 software,and the protein interaction network was analyzed by String data analysis platform.The GO enrichment analysis and KEGG pathway analysis of the core targets were performed using the online tool of gene enrichment analysis.Finally,molecular docking was used to verify the network pharmacology results.Results:A total of 78 chemical components in Heigen were identified,and 50 active components were screened.237 potential action targets were found to be associated with rheumatoid arthritis including STAT3,AKT1,EGFR and other key targets.Pathway enrichment analysis showed that PI3K-Akt,JAK-STAT may be the main pathway for Heigen to exert anti-rheumatoid arthritis.The main active components(isochlorogenic acid B,isochlorogenic acid C)were derived by molecular docking technique with good binding power to key targets.Conclusion:The study preliminarily demonstrates that the role of Heigen in the treatment of rheumatoid arthritis through multi-component,multi-target and multi-pathway,which provide a theoretical basis for the subsequent research on the substance basis of Heigen.

关 键 词：黑根 超高效液相色谱-四极杆/静电场轨道阱高分辨质谱 网络药理学 分子对接 类风湿性关节炎 

分 类 号：R285.5[医药卫生—中药学]