biostudies-literatureUnknown16(3)Junhong K<h4>Aim</h4>(-)-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.<h4>Methods</h4>An <i>in vivo</i> I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an <i>in vitro</i> 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.<h4>Results</h4>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 <i>in vivo</i>. 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 <i>in vitro</i>. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway.<h4>Conclusions</h4>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.Aging2181-2193https://www.ebi.ac.uk/biostudies/studies/S-EPMC10911377biostudies-literature(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis.PMC10911377Qian XHaowen ZYuhan DJunhong KGuangxing SYun Tfalse(-)-Epicatechin protects against myocardial ischemia/reperfusion injury via autophagy-dependent ferroptosis.<h4>Aim</h4>(-)-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.<h4>Methods</h4>An <i>in vivo</i> I/R model was constructed by performing left anterior descending coronary artery surgery on rats, and an <i>in vitro</i> 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.<h4>Results</h4>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 <i>in vivo</i>. 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 <i>in vitro</i>. Co-cultivation of USP14 inhibitor IU1 and EPI further revealed that EPI regulates ferroptosis through the USP14-autophagy pathway.<h4>Conclusions</h4>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.2024-01-01T00:00:00Z2024 Jan2025-04-05T11:38:29.077Z2025-04-05T11:38:29.077ZS-EPMC109113773827721710.18632/aging.205477