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丽妍, 李幼辰, 尤雪瑶, 姜艳艳, 刘斌.基于UPLC-Q-Exactive Orbitrap MS/MS及网络药理学探究芪风二藤汤入血成分及抗类风湿关节炎作用机制[J].湖南中医药大学学报,2026,46(2):277-287[点击复制] |
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| 基于UPLC-Q-Exactive Orbitrap MS/MS及网络药理学探究芪风二藤汤入血成分及抗类风湿关节炎作用机制 |
| 丽妍,李幼辰,尤雪瑶,姜艳艳,刘斌 |
| (北京中医药大学中药学院, 北京 102488;国家中医药管理局“中药经典名方有效物质发现”重点研究室, 北京 102488) |
| 摘要: |
| 目的 研究分析芪风二藤汤（QED）入血成分并利用网络药理学探究QED对类风湿关节炎（RA）大鼠的疗效及作用机制。方法 建立胶原诱导性关节炎（CIA）大鼠模型，随机分为模型组、雷公藤多苷片组（TGT组，0.01 g/mL）、QED水提液组（QTD-AE组，8.2 g/kg）、QED醇提液组（QTD-EE组，8.2 g/kg），每组10只；另取10只为正常组，正常组和模型组大鼠给予等体积去离子水，其余各组按剂量灌胃相应药物，均连续干预28 d。对大鼠足容积、关节炎指数进行评分，同时以HE染色对滑膜组织病理损伤程度进行分析，验证QED对RA的治疗作用。随后基于UPLC-Q-Exactive Orbitrap MS/MS技术对QED入血成分鉴定，并结合网络药理学探究QED抗RA的作用机制。结果 动物试验研究结果显示，与正常组比，模型组大鼠的足容积、关节炎指数评分及免疫器官指数明显上升（P<0.001，P<0.000 1）；与模型组比，QED可明显降低CIA大鼠足容积、关节炎指数评分及免疫器官指数（P<0.000 1）；HE染色结果显示，与模型组比，TGT组、QTD-AE组、QTD-EE组滑膜结构均趋于正常，滑膜衬里细胞局部增生，炎症细胞浸润情况减轻。通过UPLC-Q-Exactive Orbitrap MS/MS技术从QED大鼠给药血浆中鉴定出67个入血成分，其中43个为原型成分，24个为代谢产物，构建网络筛选后获得了11个核心靶点。GO富集分析和KEGG信号通路富集分析表明，QED治疗RA与Toll样受体（TLR）信号通路、肿瘤坏死因子（TNF）信号通路、白细胞介素-17（IL-17）信号通路、丝裂原活化蛋白激酶（MAPK）信号通路、RA疾病信号通路等多种信号通路等有关。分子对接结果显示，QED的核心化合物（5-O-甲基维斯阿米醇、亥茅酚、芒柄花苷、千层纸素A、青藤碱、升麻素）与治疗RA的核心靶点白细胞介素-6（IL-6）、信号转导与转录激活因子 1（STAT1）、AKT丝氨酸/苏氨酸激酶 1（AKT1）等核心靶点均有较好的结合活性。结论 QED抗RA的作用机制可能与抑制炎症反应、调节免疫等多个途径有关，从而达到治疗RA的效果。 |
| 关键词: 芪风二藤汤 UPLC-Q-Exactive Orbitrap MS/MS技术 网络药理学 类风湿关节炎 入血成分 |
| DOI：10.3969/j.issn.1674-070X.2026.02.008 |
| 投稿时间：2025-11-01 |
| 基金项目:国家中医药管理局高水平中医药重点学科建设项目:中药化学(zyyzdxk-2023258);北京中医药大学纵向课题(90020272120043)。 |
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| Blood-entry components and anti-rheumatoid arthritis mechanism of action of Qifeng Erteng Decoction based on UPLC-Q-Exactive Orbitrap MS/MS and network pharmacology |
| LI Yan, LI Youchen, YOU Xueyao, JIANG Yanyan, LIU Bin |
| (School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China;Key Laboratory of Discovery of Effective Substances in Classical Prescriptions of Traditional Chinese Medicine, National Administration of Traditional Chinese Medicine, Beijing 102488, China) |
| Abstract: |
| Objective To investigate and analyze the blood-entering components of Qifeng Fengteng Decoction (QED) and explore its therapeutic efficacy and mechanism of action in rheumatoid arthritis (RA) rats by utilizing network pharmacology. Methods The collagen-induced arthritis (CIA) rat models were established. The rats were randomly divided into several groups:model group, Tripterygium Glycosides Tablet group (TGT, 0.01 g/mL), QED aqueous extract(QTD-AE, 8.2 g/kg), and QED ethanol extract(QTD-EE, 8.2 g/kg),with 10 rats in each group. An additional 10 rats served as a normal group. The normal and model groups received an equal volume of deionized water, while the other groups were orally administered their respective medications at the designated doses for 28 consecutive days. The therapeutic effects of QED on RA were evaluated by scoring the rat paw swelling volume and arthritis index, calculating immune organ indices, and analyzing the degree of pathological damage in the synovial tissue using HE staining. Subsequently, the blood-entering components of QED were identified based on UPLC-Q-Exactive Orbitrap MS/MS technology,and the anti-RA mechanism of QED was explored using network pharmacology. Results The animal experimental results showed that compared with the normal group, the paw swelling volume, arthritis index scores, and immune organ indices of rats in the model group significantly increased (P<0.001, P<0.000 1). Compared with the model group, QED significantly reduced the paw swelling volume, arthritis index scores, and immune organ indices in CIA rats (P<0.000 1). HE staining results indicated that compared with the model group, the synovial structures in the TGT, QTD-AE, and QTD-EE groups tended to be normal, showing local hyperplasia of the synovial lining cells and reduced infiltration of inflammatory cells. Using UPLC-Q-Exactive Orbitrap MS/MS technology, 67 blood-entering components were identified in the plasma of QED-administered rats, including 43 prototype components and 24 metabolites. Network analysis screened and identified 11 core targets. GO enrichment analysis and KEGG signaling pathway enrichment analysis indicated that the treatment of RA by QED is related to multiple signaling pathways, including the Toll-like receptor (TLR) signaling pathway, tumor necrosis factor (TNF) signaling pathway, interleukin-17 (IL-17) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway,and the RA disease signaling pathway. Molecular docking results showed that the core compounds of QED (5-O-methylvisamminol, hamaudol,ononin, oroxylin A, sinomenine, cimifugin) had good binding activity with core targets for treating RA, such as interleukin-6 (IL-6), signal transducer and activator of transcription 1 (STAT1), and AKT serine/threonine kinase 1 (AKT1). Conclusion The mechanism by which QED exerts its anti-RA effects may involve multiple pathways, such as inhibiting inflammatory responses and regulating immunity, thereby achieving therapeutic efficacy against RA. |
| Key words: Qifeng Erteng Decoction UPLC-Q-Exactive Orbitrap MS/MS technology network pharmacology rheumatoid arthritis blood-entry component |
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