Guan Rui, Yao Jiashu, Qi Qing, Yu Jing, Liu Ruoshi, Gao Mingli
Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Rheumatology Department, The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Comb Chem High Throughput Screen. 2025;28(5):872-882. doi: 10.2174/0113862073296957240312090935.
This study aimed to investigate the mechanism of Si Shen Decoction (SSD) in rats with Collagen-Induced Arthritis (CIA).
Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral symmetrical multi-joint pain and swelling. SSD has shown good results in treating RA in clinical applications, but its mechanism of action remains unclear.
To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA).
Bioinformatics and network pharmacology analyses were used to predict the possible treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase chain reaction were used to verify the mechanism of SSD in the treatment of RA.
FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD group also significantly reduced the serum secretion of CRP, TNFα, and IL1β, decreased mRNA levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The therapeutic effect of SSD was significant with the increase of dose.
SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.
本研究旨在探讨四神汤（SSD）对胶原诱导性关节炎（CIA）大鼠的作用机制。
类风湿性关节炎（RA）是一种复杂的免疫疾病，其特征为双侧对称性多关节疼痛和肿胀。四神汤在临床应用中治疗RA已显示出良好效果，但其作用机制尚不清楚。
研究四神汤对胶原诱导性关节炎（CIA）大鼠的作用机制。
采用生物信息学和网络药理学分析预测可能的治疗靶点和信号通路。运用酶联免疫吸附测定（ELISA）、蛋白质印迹法和定量实时聚合酶链反应来验证四神汤治疗RA的机制。
脂肪酸结合蛋白4（FABP4）、基质金属蛋白酶9（MMP9）和前列腺素内过氧化物合酶2（PTGS2）是最常见的预测治疗靶点。四神汤治疗显著减轻了CIA大鼠的滑膜炎、踝关节肿胀和骨质侵蚀。四神汤组还显著降低了血清中C反应蛋白（CRP）、肿瘤坏死因子α（TNFα）和白细胞介素1β（IL1β）的分泌，降低了滑膜中FABP4、IKKα和p65的mRNA水平，但增加了过氧化物酶体增殖物激活受体γ（PPARγ）。蛋白质印迹法显示，四神汤治疗可显著降低滑膜中FABP4、IKKα和磷酸化p65（p-p65）蛋白的表达。发现四神汤可抑制FABP4/PPARγ/核因子κB（NFκB）信号通路，并减轻CIA大鼠的炎症反应。随着剂量增加，四神汤的治疗效果显著。
四神汤可缓解CIA大鼠的关节症状，并通过抑制FABP4/PPARγ/NFκB信号通路减轻炎症。高剂量四神汤的效果更显著。
