Immunomodulatory mechanism of Huangqi-Guizhi-Wuwu Decoction in alleviating autoimmune arthritis based on network pharmacology and experimental validation

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-01 DOI:10.1016/j.phymed.2025.156644

Wenbo Zhang , Ping Wu , Yue Song , Dandan Liang , Guangxun Meng , Huasong Zeng

{"title":"Immunomodulatory mechanism of Huangqi-Guizhi-Wuwu Decoction in alleviating autoimmune arthritis based on network pharmacology and experimental validation","authors":"Wenbo Zhang , Ping Wu , Yue Song , Dandan Liang , Guangxun Meng , Huasong Zeng","doi":"10.1016/j.phymed.2025.156644","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Purpose</h3><div>To investigate the active components of HGWD using a novel comprehensive strategy and clarify the mechanism underlying immunomodulation.</div></div><div><h3>Methods</h3><div>The main active components of HGWD were determined using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UPLC<img>HRMS). 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 <em>in vitro</em> and <em>in vivo</em> experiments.</div></div><div><h3>Results</h3><div>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 <em>in vitro</em> experiment confirmed the immunoregulatory effects of HGWD. <em>in vivo</em> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"143 ","pages":"Article 156644"},"PeriodicalIF":6.7000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Phytomedicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0944711325002843","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

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.

Abstract Image

查看原文本刊更多论文

黄芪桂枝五物汤缓解自身免疫性关节炎免疫调节机制的网络药理学研究及实验验证

背景：幼年特发性关节炎（JIA）是儿童自身免疫性关节炎中最常见的类型。黄芪桂枝五物汤（HGWD）是一种传统的中草药配方，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控机制尚不清楚。目的采用一种新的综合策略研究HGWD的有效成分，阐明其免疫调节机制。方法采用超高效液相色谱-高分辨质谱法（UPLCHRMS）测定其主要有效成分。结合网络药理学和分子对接分析，预测HGWD缓解JIA的核心靶点和生物免疫调节机制，并进行体外和体内实验。结果hplc - ms共鉴定出1387种有效成分，其中8种为主要有效成分。网络药理学表明，HGWD作用于核心靶点，如STAT3。进一步联合分析发现，调控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的关键组分能够稳定结合JAK/ stat相关蛋白。体外实验对Th17和Treg的诱导分化证实了HGWD的免疫调节作用。在体内实验中，HGWD显著缓解了胶原诱导关节炎（CIA）小鼠模型的关节炎症状，并与恢复Th17/Treg平衡密切相关。结论血清成分/UPLC-MS分析、网络药理学分析和分子生物学分析是探索黄芪有效成分的可行策略。本研究强调了HGWD在缓解JIA方面的临床潜力，并为其通过免疫调节的治疗潜力提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.