Research Paper Volume 16, Issue 3 pp 2181—2193

(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis

Kong Junhong1, *, , Tsai Yun2, *, , Shui Guangxing3, *, , Ding Yuhan2, , Xiang Qian2, , Zhang Haowen2, ,

  • 1 Nanjing University of Chinese Medicine Affiliated Changzhou Hospital, Changzhou 213000, Jiangsu, China
  • 2 Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, China
  • 3 Department of Nephrology, Shanghai Jiading Hospital of Traditional Chinese Medicine, Shanghai 201899, China
* Equal contribution

Received: May 6, 2023       Accepted: December 12, 2023       Published: January 25, 2024
How to Cite

Copyright: © 2024 Junhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aim: (-)-Epicatechin (EPI) has physiological activities such as antioxidant, anti-inflammatory and immune enhancement. In this study, we elucidated the protective effects of EPI in myocardial ischemia/reperfusion injury (MI/RI) and its mechanisms.

Methods: An in vivo I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an in vitro I/R model was constructed by subjecting hypoxia/reperfusion treatment on H9C2 cells. The damage of cardiac tissues was detected by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (H&E) staining, and expressions of ferroptosis-related proteins were examined by Western blot. Changes in the number of autophagosomes, the levels of oxidative stress and Fe2+ were also examined.

Results: EPI reduced abnormal electrocardiogram waveform and infarct size caused by MI/RI in rats. The increasing trend of levels of reactive oxygen species (ROS) and Fe2+ was reversed by EPI, suggesting that EPI can reduce ferroptosis in vivo. Moreover, the levels of lipid ROS and LC3 in H9C2 cells were decreased with EPI treatment, and autophagy and ferroptosis were also alleviated in a dose-dependent manner in vitro. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway.

Conclusions: EPI can reduce the level of oxidative stress by promoting USP14 to reduce autophagy, thus inhibiting autophagy dependent ferroptosis and reducing oxidative stress, and has a protective effect on myocardial infarction/myocardial infarction.


DHE: dihydroethidium; DIL: diltiazem; EPI: (-)-Epicatechin; FBS: fetal bovine serum; FTH1: ferritin heavy chain 1; GFP: green fluorescent protein; I/R: ischemia reperfusion; LC3: light chain 3; MDA: malondialdehyde; MIRI: myocardial ischemia reperfusion injury; NCOA4: nuclear receptor coactivator; OGD/R: oxygen-glucose deprivation/regain; ROS: reactive oxygen species; SOD: superoxide dismutase; TTC: 2,3,5-Triphenyltetrazolium chloride; TfR1: transferrin receptor 1.