2. Academic Validation
  3. Carnosic acid protects against mitochondrial dysfunction and ferroptosis in myocardial ischemia/reperfusion injury through mediating Mfn2

Carnosic acid protects against mitochondrial dysfunction and ferroptosis in myocardial ischemia/reperfusion injury through mediating Mfn2

  • Eur J Pharmacol. 2026 Mar 28:1019:178690. doi: 10.1016/j.ejphar.2026.178690.
Xiu-Qi Wang 1,  Fa-Jia Hu 1,  Huang Huang 2,  Chen-Chao Zou 1,  Yong Yuan 1,  Ya-Mei Qiao 3,  Lan-Xiang Liu 3,  Hua-Xi Zou 1,  Ji-Chun Liu 4,  Song-Qing Lai 5
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 2 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 3 School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
  • 4 Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China. Electronic address: [email protected].
  • 5 Department of Cardiovascular Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China. Electronic address: [email protected].
PMID: 41765272 DOI: 10.1016/j.ejphar.2026.178690
Abstract

The pathogenesis of myocardial ischemia/reperfusion injury (MIRI) is complicated and involves various factors, including iron overload, oxidative stress, mitochondrial damage, calcium overload, and inflammation. Hence, the aim of this study was to explore the molecular mechanisms of MIRI and verify the myocardial protection mechanism of carnosic acid (CA) in MIRI. In vivo and in vitro MIRI models were established. The results of this study verified that pretreatment with CA effectively increased cell viability, reduced the Apoptosis rate and Lactate Dehydrogenase activity, maintained mitochondrial dynamic balance, and inhibited iron overload and abnormal lipid metabolism in cardiomyocytes with anoxia/reoxygenation treatment. Pretreatment with CA not only improved cardiac function and reduced infarct size in rats treated with ischemia/reperfusion (I/R) but also decreased Reactive Oxygen Species levels and the rate of apoptotic cardiomyocytes in myocardium induced by I/R. These cardioprotective effects of CA could be inhibited by treatment with adenoviral vector expressing Mfn2 short hairpin RNA. In general, CA pretreatment protected cardiomyocytes against MIRI injury by inhibiting Ferroptosis and maintaining mitochondrial dynamic homeostasis through an Mfn2-dependent mechanism.

Keywords

Carnosic acid; Ferroptosis; Mfn2; Mitochondrial fusion/fission; Myocardial ischemia/reperfusion injury.

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