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目的 采用网络药理学和分子对接技术，探讨络石藤治疗类风湿关节炎的作用机制。方法 从Herb数据库中获得络石藤的主要成分，将获得的成分在TCMSP数据库中根据口服生物利用度和类药性进行筛选。将筛选出的成分在SymMap中进行基因靶点的筛选。从DisGeNet数据库中获取类风湿关节炎相关基因，利用Venny在线平台绘制络石藤-类风湿关节炎的交集靶点。在STRING数据库中对交集靶点进行分析，得到蛋白-蛋白相互作用网络图。采用Cytoscape分析相互作用关系并创建络石藤活性成分-类风湿关节炎网络图，并对核心靶点进行分析。通过DAVID数据库对络石藤治疗类风湿关节炎的潜在靶点进行GO功能富集分析和KEGG信号通路富集分析。在PubChem中检索并下载活性成分的分子结构，通过Chem3D将其转化为3D结构。从Uniprot和PDB数据库下载该蛋白的分子结构。采用Auto Dock Tools和Auto Dock Vina软件进行分子对接，分析结果用Pymol进行可视化。结果 络石藤的主要活性成分为伊波加因、豆甾醇、去甲汉黄芩素、菜子甾醇、谷固醇、木犀草素和牛蒡子苷，作用靶点175个，类风湿关节炎靶点867个，络石藤-类风湿交集靶点63个。Cytoscape进行PPI分析后，Degree值排名前5的核心靶点为TNF、IL-6、ALB、MMP9、AKT1。GO功能富集分析和KEGG信号通路富集分析显示，络石藤治疗类风湿关节炎主要通过PI3K-Akt信号通路、糖尿病并发症中的AGE-RAGE信号通路、癌症中的Pathways等发挥作用。根据分子对接结果，伊波加因、豆甾醇、去甲汉黄芩素、菜子甾醇、谷固醇、木犀草素和牛蒡子苷中部分成分与核心靶点对接活性良好。结论 络石藤中的活性成分伊波加因、豆甾醇、去甲汉黄芩素、菜子甾醇、谷固醇、木犀草素和牛蒡子苷参与调节PI3K-Akt信号通路、糖尿病并发症中的AGE-RAGE信号通路等，调控细胞凋亡、抑制炎性反应、调节免疫等过程治疗类风湿关节炎。
Abstract：Objective To elucidate the molecular mechanisms by which Trachelospermi Caulis exerts therapeutic effects on rheumatoid arthritis(RA) using network-pharmacology and molecular-docking approaches.Methods Major constituents of Trachelospermi Caulis were retrieved from the HERB database and filtered in TCMSP according to oral bioavailability and drug-likeness. Potential gene targets of the screened compounds were obtained from SymMap, while RA-related genes were collected from DisGeNET. Intersection targets were identified with Venny and imported into STRING to construct a protein-protein interaction(PPI) network. Cytoscape was used to visualize the Trachelospermi Caulis-compound-target-RA network and to determine hub genes. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed via the DAVID database. Structures of the active compounds were downloaded from PubChem and energy-minimized in Chem3D; crystal structures of hub proteins were obtained from UniProt and the Protein Data Bank. AutoDockTools and AutoDock Vina were employed for molecular-docking studies, and binding conformations were visualized with PyMOL.Results Seven key bioactive compounds—ibogamine, stigmasterol, norwogonin, brassicasterol, sitosterol, luteolin, and arctiin—were identified, corresponding to 175 putative targets. A total of 867 RA-associated genes were collected; 63 overlapped with the compound targets. PPI analysis indicated TNF, IL-6, ALB, MMP9, and AKT1 as the top five hub proteins(highest degree values). GO and KEGG results suggested that Trachelospermi Caulis primarily modulates the PI3K-Akt pathway, the AGE-RAGE signalling pathway in diabetic complications, and multiple cancer-related pathways, implicating processes such as apoptosis regulation, inflammatory suppression, and immune modulation. Molecular-docking scores showed strong binding affinities between each of the seven core compounds and the identified hub proteins, supporting their potential synergistic actions.Conclusion Ibogamine, stigmasterol, norwogonin, brassicasterol, sitosterol, luteolin, and arctiin in Caulis Trachelospermi appear to alleviate RA by targeting key nodes(TNF, IL-6, ALB, MMP9, AKT1) within the PI3K-Akt, AGE-RAGE, and other signalling pathways, thereby regulating apoptosis, inhibiting inflammation, and modulating immune responses.
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基本信息:
DOI：
中图分类号:R259
引用信息:
[1]高元元,宋梓源,凌益等.络石藤治疗类风湿关节炎的作用机制：网络药理学视角[J].微量元素与健康研究,2025,42(04):4-11.
基金信息:
国家自然科学基金项目(82274678); 青年科学基金项目(82405366); 贵州省科技计划项目(黔科合基础-ZK[2024]一般416); 2024年度贵州省卫生健康委科学技术基金项目(gzwkj2024-354); 贵州中医药大学研究生创新项目(YCXKYB2023010); 贵州省教育厅高等学校自然科学研究项目(青年科技人才成长项目)(黔教技[2024]118号)