Buyang Huanwu Decoction suppresses atherosclerosis by targeting IFITM1‑mediated lipid metabolism in vascular smooth muscle cells

  • Phytomedicine. 2026 Jul:156:158224. doi: 10.1016/j.phymed.2026.158224.
Qionghui Huang  1 ,  Xiaoyan Tang  1 ,  Qingyan Huang  2 ,  Shaobin Zhi  2 ,  Xiaoqi Zheng  3 ,  Qiaoting Deng  2 ,  Junxing Zhu  4 ,  Mingfeng Huang  5 ,  Zengfeng Pan  6 ,  Jingyuan Hou  7
Affiliations
  • 1. Institute of Cardiovascular Disease, Affiliated Meizhou Hospital of Shantou University Medical College, Meizhou, China; GuangDong Engineering Technological Research Center of Molecular Diagnosis in Cardiovascular Diseases, Meizhou, China.
  • 2. Institute of Cardiovascular Disease, Affiliated Meizhou Hospital of Shantou University Medical College, Meizhou, China.
  • 3. Institute of Basic Medical Sciences, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China.
  • 4. Center for Cardiovascular Diseases, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China.
  • 5. Institute of Basic Medical Sciences, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China. Electronic address: [email protected].
  • 6. Institute of Basic Medical Sciences, Meizhou People's Hospital, Meizhou Academy of Medical Sciences, Meizhou, China. Electronic address: [email protected].
  • 7. Institute of Cardiovascular Disease, Affiliated Meizhou Hospital of Shantou University Medical College, Meizhou, China; GuangDong Engineering Technological Research Center of Molecular Diagnosis in Cardiovascular Diseases, Meizhou, China. Electronic address: [email protected].
PMID: 42030801 DOI: 10.1016/j.phymed.2026.158224
Abstract

Background: The transformation of vascular smooth muscle cells (VSMCs) into foam cells is a pivotal event in atherosclerotic plaque formation during atherosclerosis. Although interferon-induced transmembrane protein 1 (IFITM1) represents a key regulator across diverse diseases, its specific contribution in VSMCs and its involvement in atherosclerosis remain insufficiently explored. Buyang Huanwu Decoction (BYHWD), a traditional Chinese medicinal formulation, has been demonstrated to be effective against atherosclerosis; however, the underlying mechanisms warrants further elucidation.

Purpose: This research sought to assess BYHWD's impact on VSMC-originated foam cell generation in atherosclerosis and to decipher its mechanistic basis, particularly focusing on IFITM1 downregulation.

Methods: BYHWD was administered to HFD-fed apoE-/- mice, and its effects were evaluated through lipid profiling, Oil Red O staining, immunofluorescence, and western blot analyses. Additionally, transcriptomic profiling was conducted to delineate differentially expressed genes and potential pathways affected in atherosclerosis following BYHWD treatment. Involvement of IFITM1 in driving VSMC-derived foam cells generation was investigated using IFITM1-overexpressing and IFITM1-knockdown cells, as well as IFITM1-/- mice. Furthermore, coadministration of an adeno-associated virus (AAV) expressing IFITM1 with BYHWD was undertaken to elucidate their interaction in atherosclerotic pathogenesis.

Results: BYHWD markedly reduced plaque area and lipid accumulation. Microarray analysis revealed that BYHWD treatment potently suppressed IFITM1 gene expression in atherosclerotic tissues. Elevated levels of IFITM1 were observed in plaque samples from atherosclerotic patients and in VSMCs treated with oxidized low-density lipoprotein (ox-LDL). IFITM1 depletion mitigated Cholesterol accumulation, while IFITM1 overexpression could partially negate the atherosclerosis -inhibitory property of BYHWD. Mechanistically, BYHWD ameliorated atherosclerosis by targeting IFITM1-mediated AMPK/PPARγ/ABCA1 pathway.

Conclusion: Our findings indicate that BYHWD significantly mitigates the development of atherosclerosis by inhibiting IFITM1 and upregulating downstream AMPK/PPARγ/ABCA1 signaling. These results suggest that BYHWD, as an inhibitor of IFITM1, may represent a novel therapeutic approach for atherosclerosis intervention.

Keywords
AMPK/PPARγ/ABCA1 pathway; Atherosclerosis; BYHWD; IFITM1; VSMCs.
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