2. Academic Validation
  3. Cardamonin inhibits atrial remodeling in mice by upregulating the expression of USP18

Cardamonin inhibits atrial remodeling in mice by upregulating the expression of USP18

  • Phytomedicine. 2025 Dec:149:157512. doi: 10.1016/j.phymed.2025.157512.
Zhenyu Feng 1,  Yiheng Yang 1,  Wenjun Zheng 2,  Jie Bai 3,  Qiu-Yue Lin 1,  Yijin Yang 1,  Ningning Zhang 4,  Yun-Long Xia 5,  Yunpeng Xie 6
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Diseases, The first affiliated Hospital of Dalian Medical University, Dalian, , People's Republic of China.
  • 2 Department of Cardiovascular Surgery, The first affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
  • 3 Department of Occupational and Environmental Health, School of Public Health, Dalian Medical University, Dalian, People's Republic of China.
  • 4 Department of Hematology, the First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China. Electronic address: [email protected].
  • 5 Institute of Cardiovascular Diseases, The first affiliated Hospital of Dalian Medical University, Dalian, , People's Republic of China. Electronic address: [email protected].
  • 6 Institute of Cardiovascular Diseases, The first affiliated Hospital of Dalian Medical University, Dalian, , People's Republic of China. Electronic address: [email protected].
PMID: 41240540 DOI: 10.1016/j.phymed.2025.157512
Abstract

Background: Atrial fibrillation is primarily driven by atrial remodeling. Cardamonin, extracted from ancient Chinese remedies, has a beneficial effect on heart health. However, it is still needed to investigate the specific effects of Cardamonin on atrial remodeling.

Methods: We utilized Ang II to induce atrial fibrillation. Different doses of Cardamonin were administered to mice. AAV9-cTNT-USP18 and myocardial-specific knockout of USP18 were constructed. Through echocardiography, electrical stimulation, qPCR and pathological staining, the roles of CAR and USP18 in atrial remodeling were demonstrated. amiodarone was the positive control for observing the anti- atrial fibrillation effects of CAR. The indirect relationship between CAR and USP18 was found by various Molecular Biology experiments RESULTS: The findings indicated that Cardamonin effectively decreased the occurrence and duration of AF induced by Ang II, as well as lowered levels of atrial fibrosis, inflammation, and oxidative stress. Overexpression of USP18 could promote the inhibitory effect of Cardamonin on Ang II-induced incidence and duration of AF, and significantly suppressing atrial remodeling in mice. In contrast, knockout of USP18 significantly interfered with the anti-atrial remodeling effect of Cardamonin, increasing atrial remodeling. The anti-remodeling effect of CAR on the atrium is comparable to that of amiodarone. At the same time, it was found that CAR may bind to NRF2 to regulate the transcription level of USP18. USP18 may interact with SERCA2.

Conclusions: These results not only clarify that Cardamonin regulates atrial remodeling through USP18, but also provide a theoretical basis for the development of new and safe therapeutic drugs for atrial remodeling, opening up new avenues for the treatment of cardiovascular diseases and bringing hope for more effective and safer treatment options.

Keywords

Ang II; Atrial remodeling; Cardamonin; USP18.

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