目的 研究光叶丁公藤Erycibe schmidtii与3个潜在代用品多花丁公藤E.myriantha、凹脉丁公藤E.elllptilimba、大果飞蛾藤Porana sinensis治疗类风湿性关节炎（rheumatoid arthritis，RA）的差异性成分和潜在作用机制。方法 采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法（UHPLC-Q Exactive Focus MS/MS）分析光叶丁公藤及3个潜在代用品的差异成分；结合Swiss Target Prediction、DisGeNET、OMIM、TTD等数据库获得差异成分治疗RA的作用靶点；采用STRING数据库构建共有靶点互作（protein-protein interaction，PPI）网络模型，采用Cytoscape 3.6.0软件进行可视化处理并分析网络拓扑参数筛选出核心靶点；通过DAVID数据库和R语言软件对靶点进行基因本体（gene ontology，GO）分析和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）信号通路富集分析，采用Cytoscape 3.6.0软件构建“药材-差异成分-靶点-通路（H-C-T-P）”网络图并进行分析，探讨光叶丁公藤及3个潜在代用品差异成分治疗RA的潜在作用机制。结果 从光叶丁公藤及3个潜在代用品中共鉴定60个成分，其中差异成分35个，共涉及348个靶点。与RA相关的差异成分有18个，得到差异成分-RA共同靶点153个。GO和KEGG富集分析结果显示光叶丁公藤及3个潜在代用品可能通过芒柄花素、丁公藤黄素E、圣草酚、N-反式-对香豆酰酪胺、秦皮乙素共5个活性差异成分作用于RAC-α丝氨酸/苏氨酸蛋白激酶（RAC-alpha serine/threonine-protein kinase，AKT1）、双特异性丝裂原活化蛋白激酶激酶1（dual specificity mitogen-activated protein kinase kinase 1，MAP2K1）、磷脂酰肌醇4,5-二磷酸3-激酶催化亚单位α亚型（phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform，PIK3CA）等32个靶点，调节PI3K-Akt信号通路、Rap1信号通路、Ras信号通路等5个信号通路发挥治疗RA的作用。结论 初步明确了光叶丁公藤及3个潜在代用品治疗RA的差异成分、关键靶点和核心通路；光叶丁公藤和大果飞蛾藤所鉴定的共有化学成分数量和H-C-T-P网络图中度值较其他2个潜在代用品高，说明大果飞蛾藤更适合做光叶丁公藤代用品；为濒危中药代用品开发提供了相对可靠的新策略。

Objective To clarify the discriminatory compounds and action mechanism of Erycibe schmidtii Craib and three potential substitutes against rheumatoid arthritis (RA). Methods The discriminatory compounds between E. schmidtii and three potential substitutes were analyzed by UHPLC-Q Exactive Focus MS/MS. Combined with Swiss target prediction and DisGeNET, OMIM, TTD databases, the common targets for discriminatory compounds in the treatment of RA was obtained. The common targets were imported into the STRING database to construct the network diagram of target interaction, and Cytoscape 3.6.0 software was used to screen out the core targets. The GO and KEGG enrichment analysis of the target were carried out by DAVID database and R language software. The network diagram of Herb-Component-Target-Passway (H-C-T-P) was constructed by Cytoscape 3.6.0 software and analyzed to explore the potential mechanism of the discriminatory components of E. schmidtii and three potential substitutes against RA.Results A total of 60 components were identified from E. schmidtii and three potential substitutes, including 35 discriminatory components, involving 348 targets. There were 18 components related to RA, and there were 153 common targets for the discriminatory components and RA. GO and KEGG pathway enrichment analysis revealed that five active discriminatory components (formononetin, erycibenin E, eriodictyol, N-p-trans-coumaroyltyramine and esculetin) of E. schmidtii and three potential substitutes acted on AKT1, MAP2K1, PIK3CA and other 32 targets, and may regulate five pathways including PI3K-Akt, Rap1, Ras and so on. Conclusion The present study preliminarily identified the discriminatory components, key targets and core pathways of E. schmidtii and three potential substitutes in the treatment of RA. The number of common chemical components identified in E. schmidtii and P. sinensis and the degree of H-C-T-P network diagram were higher than the other two potential substitutes, which indicate that P. sinensis is more suitable than other two substitutes. This study provides a relatively reliable strategy for the development of endangered traditional Chinese medicine substitutes.

R284.1

国家自然科学基金面上项目（81973419）；陕西省重点研发计划一般项目（2022-SF-315）；陕西省中医药管理局青年培优项目（2021-PY-003）；陕西省中医药管理局项目（2021-ZZ-JC033）；陕西省中医药研究院“苗圃计划”一般项目（2021-12）