2. Academic Validation
  3. Buyang Huanwu Decoction attenuates vascular aging by suppressing the pathway of neutrophil extracellular trap formation via modulation of the HMGB1/TLR4/p38 signaling pathway

Buyang Huanwu Decoction attenuates vascular aging by suppressing the pathway of neutrophil extracellular trap formation via modulation of the HMGB1/TLR4/p38 signaling pathway

  • J Ethnopharmacol. 2026 May 10:362:121315. doi: 10.1016/j.jep.2026.121315.
Nan Xiao 1,  Jinsong Gao 2,  Yutong Yang 1,  Chenghui Li 3,  Xuejuan Shen 4,  Xiangyu Chen 1,  Xiaodie Chen 1,  Yanbin Pan 3,  Huiqun Huang 3,  Simin Yang 5,  Shuting Zeng 5,  Xiaodong Duan 5,  Yongan Deng 5,  Chengkai Chen 5,  Yixuan Huang 5,  Danping Huang 6,  Zunpeng Shu 7,  Li Zhang 8
Affiliations

Affiliations

  • 1 Cardiology Department, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, China; Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China.
  • 2 Department of Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310016, China.
  • 3 Cardiology Department, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, China.
  • 4 Nephrology and Rheumatology Department, The Affiliated TCM Hospital of Guangzhou Medical University, The Affiliated Guangzhou Hospital of TCM of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510630, China.
  • 5 Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China; School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, China.
  • 6 Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, China.
  • 7 Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, Guangdong, 519087, China. Electronic address: [email protected].
  • 8 Cardiology Department, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, China. Electronic address: [email protected].
PMID: 41655726 DOI: 10.1016/j.jep.2026.121315
Abstract

Ethnopharmacological relevance: Vascular aging is a significant driver of age-related cardiovascular diseases, in which the immune-inflammatory response driven by excessive formation of neutrophil extracellular traps (NETs) is a core process accelerating this progression. Buyang Huanwu Decoction (BHD) is a classic traditional Chinese medicine (TCM) formula widely used for treating cardio-cerebrovascular diseases, but whether it acts through modulating NET-driven vascular aging is unknown.

Aim of the study: This study aims to investigate the mechanism by which BHD delays vascular aging, focusing on the NETs formation pathway.

Materials and methods: Based on a D-galactose-induced aging mouse model, this study focused on neutrophils and combined transcriptomics, network pharmacology and Molecular Biology methods to explore the mechanism of BHD in delaying vascular aging.

Results: The present study identified 23 major chemical constituents in BHD and demonstrated its efficacy in ameliorating aging phenotypes in a D-galactose-induced aging mouse model. BHD treatment significantly alleviated aortic structural degeneration, reduced oxidative stress and inflammatory cytokine levels, and downregulated key senescence markers including p16 and p21. Integrated multi-omics analysis implicated NET suppression as a primary mechanism underlying the Anti-aging benefits of BHD. Both in vivo and in vitro experiments confirmed that BHD inhibits NETosis by modulating the HMGB1/TLR4/p38 signaling pathway, leading to reduced expression of critical NET components. Notably, HMGB1 overexpression partially reversed the inhibitory effects of BHD on NETosis, establishing HMGB1 as a key effector molecule.

Conclusion: For the first time, our findings unveil a novel mechanism whereby BHD alleviates vascular aging by modulating the immune microenvironment through inhibition of the HMGB1-TLR4-p38-NETs cascade. These findings provide a novel immunomodulatory perspective on BHD and highlight its potential as a holistic therapeutic strategy against vascular aging.

Keywords

Buyang Huanwu decoction; HMGB1/TLR4/p38 signaling pathway; Neutrophil extracellular traps (NETs); Vascular senescence.

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