Peng Muzi, Yao Zhongliu, Zhang Junlan, Lin Ye, Xu Li, Zhang Qin, Liao Jing, Cai Xiong
Department of Rheumatology of First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, China; Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, China.
Department of Rheumatology of First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, China.
J Ethnopharmacol. 2024 Jul 15;329:118140. doi: 10.1016/j.jep.2024.118140. Epub 2024 Mar 31.
Qingfu Juanbi Tang (QFJBT), a novel and improved Chinese herbal formulation, has surged in recent years for its potential in the therapy of rheumatoid arthritis (RA). Anti-arthritic effects and underlying molecular mechanisms of QFJBT have increasingly become a focal point in research.
This study utilized network pharmacology, molecular docking, and experimental validation to elucidate effective ingredients and anti-arthritic mechanisms of QFJBT.
Targets associated with QFJBT and RA were identified from relevant databases and standardized using the Uniprot for gene nomenclature. A "QFJBT-ingredient-target network" and a "Venn diagram of QFJBT and RA targets" were created from the data. The overlap in the Venn diagram highlighted potential targets of QFJBT in the treatment of RA. These targets were subjected to PPI network, GO, and KEGG pathway analysis. The findings were subsequently confirmed through molecular docking and pharmacological experiments to propose the mechanism of action of QFJBT.
The study identified 236 active ingredients in QFJBT, with 120 predicted to be effective against RA. Molecular docking showed high binding affinity of key targets (JUN, PTGS2, and TNF-α) with bioactive compounds (rhein, sinomenine, calycosin, and paeoniflorin) of QFJBT. Pharmacodynamic evaluation demonstrated the effects of QFJBT at the dose of 4.56 g/kg in ameliorating symptoms of AIA rats and in reducing levels of JUN, PTGS2, and TNF-α in synovial tissues. In vitro studies further exhibited that rhein, paeoniflorin, sinomenine, calycosin, and QFJBT-containing serum significantly inhibited abnormal proliferation of RA fibroblast-like synoviocytes. Interestingly, rhein and paeoniflorin specifically decreased p-JUN/JUN expression and TNF-α release, respectively, while sinomenine and calycosin selectively increased PTGS2 expression. Consistently, QFJBT-containing serum demonstrated similar effects as those active ingredients identified in QFJBT did.
QFJBT, QFJBT-containing serum, and its active ingredients (rhein, paeoniflorin, sinomenine, and calycosin) suppress inflammatory responses in RA. Anti-arthritic effects of QFJBT and its active ingredients are likely linked to their modulatory impact on identified hub targets.
清芙蠲痹汤（QFJBT）是一种新型改良的中药配方，近年来因其在类风湿性关节炎（RA）治疗中的潜力而备受关注。QFJBT的抗关节炎作用及其潜在的分子机制日益成为研究的焦点。
本研究利用网络药理学、分子对接和实验验证来阐明QFJBT的有效成分和抗关节炎机制。
从相关数据库中识别与QFJBT和RA相关的靶点，并使用Uniprot对基因命名进行标准化。根据数据构建了“QFJBT-成分-靶点网络”和“QFJBT与RA靶点的维恩图”。维恩图中的重叠部分突出了QFJBT在治疗RA中的潜在靶点。对这些靶点进行蛋白质-蛋白质相互作用（PPI）网络、基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。随后通过分子对接和药理学实验对研究结果进行确认，以提出QFJBT的作用机制。
该研究在QFJBT中鉴定出236种活性成分，其中120种预计对RA有效。分子对接显示关键靶点（JUN、PTGS2和TNF-α）与QFJBT的生物活性化合物（大黄酸、青藤碱、毛蕊异黄酮和芍药苷）具有高结合亲和力。药效学评价表明，4.56 g/kg剂量的QFJBT可改善佐剂性关节炎（AIA）大鼠的症状，并降低滑膜组织中JUN、PTGS2和TNF-α的水平。体外研究进一步表明，大黄酸、芍药苷、青藤碱、毛蕊异黄酮和含QFJBT血清可显著抑制RA成纤维样滑膜细胞的异常增殖。有趣的是，大黄酸和芍药苷分别特异性降低p-JUN/JUN表达和TNF-α释放，而青藤碱和毛蕊异黄酮选择性增加PTGS2表达。一致地，含QFJBT血清表现出与QFJBT中鉴定出的活性成分相似的作用。
QFJBT、含QFJBT血清及其活性成分（大黄酸、芍药苷、青藤碱和毛蕊异黄酮）可抑制RA中的炎症反应。QFJBT及其活性成分的抗关节炎作用可能与其对已确定的枢纽靶点的调节作用有关。
