Li Zhan-Hua, Chen Si-Ning, Pan Ling, Liu Rui, Liang Wei, Luo Mei-Qun, Liao Hai-Fei, Feng Jie, Wang Hao-Zhou, Huang Yue-Gan, Zheng Jing-Hui
Department of Respiratory and Critical Care Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People's Republic of China.
Academic Affairs Office, Guangxi University of Chinese Medicine, Nanning, Guangxi, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2025 Jul 5;20:2227-2247. doi: 10.2147/COPD.S512469. eCollection 2025.
Chronic Obstructive Pulmonary Disease (COPD) is chronic respiratory disease that severely affects patients' quality of life and is associated with high mortality rates. Investigating the imbalance between regulatory T cells (Tregs) and T helper 17 cells (Th17) in COPD treatment is crucial, as this imbalance plays a significant role in the disease's inflammatory processes. This study explores the therapeutic potential of the traditional Chinese medicine(TCM) formula, Lijin Fang (LJF), focusing on its ability to restore Treg/Th17 balance.
We employed bioinformatics and in vitro cell experiments to analyze the active components and targets of LJF. Network pharmacology, differential gene expression, pathway enrichment, ROC model prediction, and immune infiltration analyses were conducted, followed by molecular docking studies. Rat peripheral blood mononuclear cells (PBMCs) were cultured and treated with cigarette smoke extract (CSE) and LJF-containing serum, with flow cytometry, ELISA, and Western blotting used to assess relevant markers.
Our findings demonstrate that treatment with (10% or 30%)LJF-containing serum significantly increased the proportion of Treg cells while concurrently decreasing Th17 cell populations in the 5%CSE-treated rat PBMC model (p<0.001). We observed a reduction in pro-inflammatory cytokines such as interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), alongside an increase in the anti-inflammatory cytokine interleukin-10 (IL-10) (p<0.001). Additionally, potential therapeutic targets, including IL-10, potassium voltage-gated channel subfamily N member 4 (KCNN4), and Baculoviral IAP repeat-containing protein 3 (BIRC3), were identified. Molecular docking results indicated stable interactions between IL-10 and BIRC3 with the constituents of LJF.
This study highlights LJF's anti-inflammatory potential in restoring the Treg/Th17 balance and regulating cytokine expression in COPD.
慢性阻塞性肺疾病（COPD）是一种严重影响患者生活质量且死亡率较高的慢性呼吸道疾病。研究COPD治疗中调节性T细胞（Tregs）和辅助性T细胞17（Th17）之间的失衡至关重要，因为这种失衡在该疾病的炎症过程中起重要作用。本研究探讨了中药方剂理金方（LJF）的治疗潜力，重点关注其恢复Treg/Th17平衡的能力。
我们采用生物信息学和体外细胞实验分析LJF的活性成分和靶点。进行了网络药理学、差异基因表达、通路富集、ROC模型预测和免疫浸润分析，随后进行分子对接研究。培养大鼠外周血单核细胞（PBMCs），并用香烟烟雾提取物（CSE）和含LJF的血清进行处理，采用流式细胞术、酶联免疫吸附测定（ELISA）和蛋白质免疫印迹法评估相关标志物。
我们的研究结果表明，在5%CSE处理的大鼠PBMC模型中，用含（10%或30%）LJF的血清处理显著增加了Treg细胞的比例，同时降低了Th17细胞群体（p<0.001）。我们观察到促炎细胞因子如白细胞介素-17（IL-17）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）减少，同时抗炎细胞因子白细胞介素-10（IL-10）增加（p<0.001）。此外，还确定了潜在的治疗靶点，包括IL-10、钾电压门控通道亚家族N成员4（KCNN4）和含杆状病毒IAP重复序列蛋白3（BIRC3）。分子对接结果表明IL-10和BIRC3与LJF的成分之间存在稳定的相互作用。
本研究突出了LJF在恢复COPD中Treg/Th17平衡和调节细胞因子表达方面的抗炎潜力。
