Integrated transcriptome and metabolome analysis reveals the therapeutic mechanism of Huang-Qi-Si-Wu-Tang in experimental pulmonary arterial hypertension

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-07 DOI:10.1016/j.phymed.2025.157058

Ye Wang , Zhuangjie Guo , Xinqi Ma , Qing Xu , Dandan Li , Jie Yang , Xiaoxuan Lu , Peiran Yang , Hongchun Zhang , Hongmei Zhao , Chen Wang

{"title":"Integrated transcriptome and metabolome analysis reveals the therapeutic mechanism of Huang-Qi-Si-Wu-Tang in experimental pulmonary arterial hypertension","authors":"Ye Wang , Zhuangjie Guo , Xinqi Ma , Qing Xu , Dandan Li , Jie Yang , Xiaoxuan Lu , Peiran Yang , Hongchun Zhang , Hongmei Zhao , Chen Wang","doi":"10.1016/j.phymed.2025.157058","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Pulmonary arterial hypertension is a complex vascular disease involving pathological remodeling of vascular cells, inflammatory cells, and the extracellular matrix. Current PAH therapies, which are primarily vasodilators, cannot reverse the disease pathogenesis or cure PAH. Novel therapeutic agents targeting the core process of vascular remodeling are desperately needed, and their mechanisms warrant systematic investigation.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the therapeutic potential of Huang-Qi-Si-Wu-Tang (HQSWT), a traditional Chinese herbal formula, in experimental models of PAH and to elucidate its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We used monocrotaline-induced PAH in rats as an experimental model. We assessed the effect of HQSWT on disease prevention, as well as its effect in mitigating established disease. We employed RNA sequencing, integrated metabolomics and transcriptomics analysis, and validated findings by multiplex immunohistochemistry and quantitative PCR.</div></div><div><h3>Results</h3><div>HQSWT dose-dependently prevented monocrotaline-induced PAH development and mitigated established PAH, right ventricular hypertrophy, and pulmonary vascular remodeling. Transcriptomic analysis revealed HQSWT’s action on extracellular matrix pathways, including <em>Fn1</em> and <em>Thbs2</em>. Furthermore, we observed modulation of arachidonic acid metabolism via the ALOX5-LTB<sub>4</sub> axis. HQSWT reduced ALOX5 expression in lung tissue and perivascular macrophages.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that HQSWT is effective in treating experimental PAH. Through omics analysis, we have identified a novel mechanism of action whereby HQSWT may exert its protective effects by simultaneously targeting the extracellular matrix and inflammation-mediated pulmonary vascular remodeling, suggesting its potential as a new therapy for PAH.</div></div>","PeriodicalId":20212,"journal":{"name":"Phytomedicine","volume":"145 ","pages":"Article 157058"},"PeriodicalIF":6.7000,"publicationDate":"2025-07-07","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/S094471132500697X","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

Pulmonary arterial hypertension is a complex vascular disease involving pathological remodeling of vascular cells, inflammatory cells, and the extracellular matrix. Current PAH therapies, which are primarily vasodilators, cannot reverse the disease pathogenesis or cure PAH. Novel therapeutic agents targeting the core process of vascular remodeling are desperately needed, and their mechanisms warrant systematic investigation.

Purpose

This study aimed to investigate the therapeutic potential of Huang-Qi-Si-Wu-Tang (HQSWT), a traditional Chinese herbal formula, in experimental models of PAH and to elucidate its underlying mechanisms.

Methods

We used monocrotaline-induced PAH in rats as an experimental model. We assessed the effect of HQSWT on disease prevention, as well as its effect in mitigating established disease. We employed RNA sequencing, integrated metabolomics and transcriptomics analysis, and validated findings by multiplex immunohistochemistry and quantitative PCR.

Results

HQSWT dose-dependently prevented monocrotaline-induced PAH development and mitigated established PAH, right ventricular hypertrophy, and pulmonary vascular remodeling. Transcriptomic analysis revealed HQSWT’s action on extracellular matrix pathways, including Fn1 and Thbs2. Furthermore, we observed modulation of arachidonic acid metabolism via the ALOX5-LTB₄ axis. HQSWT reduced ALOX5 expression in lung tissue and perivascular macrophages.

Conclusion

Our results demonstrate that HQSWT is effective in treating experimental PAH. Through omics analysis, we have identified a novel mechanism of action whereby HQSWT may exert its protective effects by simultaneously targeting the extracellular matrix and inflammation-mediated pulmonary vascular remodeling, suggesting its potential as a new therapy for PAH.

Abstract Image

查看原文本刊更多论文

综合转录组和代谢组分析揭示黄芪四物汤治疗实验性肺动脉高压的机制

肺动脉高压是一种复杂的血管疾病，涉及血管细胞、炎症细胞和细胞外基质的病理性重塑。目前的多环芳烃治疗主要是血管扩张剂，不能逆转疾病的发病机制或治愈多环芳烃。针对血管重构核心过程的新型治疗药物是迫切需要的，其机制需要系统的研究。目的探讨中药黄芪四物汤对多环芳烃（PAH）模型的治疗作用，并探讨其作用机制。方法以大鼠多环芳烃为实验模型。我们评估了HQSWT在疾病预防方面的作用，以及它在减轻既定疾病方面的作用。我们采用了RNA测序、综合代谢组学和转录组学分析，并通过多重免疫组织化学和定量PCR验证了研究结果。结果shqswt呈剂量依赖性地阻止了单苦参碱诱导的PAH发展，减轻了已建立的PAH、右心室肥厚和肺血管重构。转录组学分析显示HQSWT作用于细胞外基质通路，包括Fn1和Thbs2。此外，我们还通过ALOX5-LTB4轴观察到花生四烯酸代谢的调节。HQSWT降低ALOX5在肺组织和血管周围巨噬细胞中的表达。结论HQSWT对实验性多环芳烃有较好的治疗效果。通过组学分析，我们发现了一种新的作用机制，即HQSWT可以同时靶向细胞外基质和炎症介导的肺血管重构，从而发挥其保护作用，这表明HQSWT可能是一种治疗PAH的新方法。

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.