2. Academic Validation
  3. Acacetin alleviates autoimmune myocarditis by regulating CD4+ T cell mitochondrial respiration

Acacetin alleviates autoimmune myocarditis by regulating CD4+ T cell mitochondrial respiration

  • Chin Med. 2024 May 13;19(1):68. doi: 10.1186/s13020-024-00943-9.
Yang Lu 1 2 3 4 5 6,  Yu-Wei Wu 1 2 3 4 5,  Jiu Pu 1 2 3 4 5,  Qiong-Feng Wu 1 2 3 4 5,  Qian Dong 1 2 3 4 5,  Ning Zhao 1 2 3 4 5,  Gui-Rong Li 7,  Yi-Mei Du 8 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 6 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 7 Nanjing Amazigh Pharma Limited, Nanjing, Jiangsu, China.
  • 8 Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yimeidu@mail.hust.edu.cn.
  • 9 Research Center of Ion Channelopathy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yimeidu@mail.hust.edu.cn.
  • 10 Institute of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yimeidu@mail.hust.edu.cn.
  • 11 Key Lab for Biological Targeted Therapy of Education Ministry and Hubei Province, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yimeidu@mail.hust.edu.cn.
  • 12 Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yimeidu@mail.hust.edu.cn.
PMID: 38741130 DOI: 10.1186/s13020-024-00943-9
Abstract

Background: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis.

Methods: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with Myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function.

Results: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial Reactive Oxygen Species in CD4+ T cells.

Conclusion: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis.

Keywords

Acacetin; CD4+ T cells; Mitochondrial complex II; Mitochondrial respiration; Myocarditis; Th17 cells.

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