基于网络药理学和实验验证的黄芪桂枝五物汤缓解自身免疫性关节炎的免疫调节机制
Immunomodulatory mechanism of Huangqi-Guizhi-Wuwu Decoction in alleviating autoimmune arthritis based on network pharmacology and experimental validation.
作者信息
Zhang Wenbo, Wu Ping, Song Yue, Liang Dandan, Meng Guangxun, Zeng Huasong
机构信息
The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, China; The Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China; The Joint Center for Infection and Immunity, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China.
Department of Pediatrics, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
出版信息
Phytomedicine. 2025 Jul 25;143:156644. doi: 10.1016/j.phymed.2025.156644. Epub 2025 May 1.
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common type of childhood autoimmune arthritis. Huangqi Guizhi Wuwu decoction (HGWD), a traditional Chinese herbal formula, is widely used in China to treat patients with autoimmune arthritis. However, the bioactive ingredients and their complex regulatory mechanisms remain unclear.
PURPOSE
To investigate the active components of HGWD using a novel comprehensive strategy and clarify the mechanism underlying immunomodulation.
METHODS
The main active components of HGWD were determined using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLCHRMS). The core target and biological immune regulation mechanism of HGWD in alleviating JIA were predicted using combined network pharmacology and molecular docking analyses, followed by in vitro and in vivo experiments.
RESULTS
A total of 1387 active components were identified by UPLC-MS, of which eight were the main active ingredients. Network pharmacology showed that HGWD acted on core targets, such as STAT3. Further combined analysis revealed that regulation of the Th17 differentiation pathway may be an important mechanism by which HGWD relieves JIA. Molecular docking verification showed that the key component of HGWD can stably bind JAK/STAT-related proteins. The induced differentiation of Th17 and Treg in vitro experiment confirmed the immunoregulatory effects of HGWD. in vivo experiments, HGWD significantly alleviated symptoms of arthritis in a mouse model of collagen-induced arthritis (CIA) and was closely associated with restoring the Th17/Treg balance.
CONCLUSION
Taken together, serum components/UPLC-MS, network pharmacology, and molecular biology analyses are feasible strategies for exploring the active ingredients in HGWD. This study highlights the clinical potential of HGWD in alleviating JIA and provides evidence of its therapeutic potential through immune regulation.
背景
幼年特发性关节炎（JIA）是儿童期最常见的自身免疫性关节炎类型。黄芪桂枝五物汤（HGWD）是一种传统中药配方，在中国广泛用于治疗自身免疫性关节炎患者。然而，其生物活性成分及其复杂的调节机制仍不清楚。
目的
采用一种新颖的综合策略研究HGWD的活性成分，并阐明其免疫调节的潜在机制。
方法
使用超高效液相色谱-高分辨率质谱（UPLC-HRMS）测定HGWD的主要活性成分。通过网络药理学和分子对接分析相结合的方法预测HGWD在缓解JIA中的核心靶点和生物免疫调节机制，随后进行体外和体内实验。
结果
通过UPLC-MS共鉴定出1387种活性成分，其中8种为主要活性成分。网络药理学表明HGWD作用于STAT3等核心靶点。进一步的综合分析表明，调节Th17分化途径可能是HGWD缓解JIA的重要机制。分子对接验证表明HGWD的关键成分能与JAK/STAT相关蛋白稳定结合。体外实验中HGWD诱导Th17和Treg分化证实了其免疫调节作用。在体内实验中，HGWD显著减轻了胶原诱导性关节炎（CIA）小鼠模型的关节炎症状，并且与恢复Th17/Treg平衡密切相关。
结论
综上所述，血清成分/UPLC-MS、网络药理学和分子生物学分析是探索HGWD活性成分的可行策略。本研究突出了HGWD在缓解JIA方面的临床潜力，并通过免疫调节提供了其治疗潜力的证据。
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