心肌缺血再灌注(I/R)损伤触发了多种细胞死亡类型，包括凋亡、自噬和铁死亡。甘草花黄酮甲素(LCA)是一种从甘草根中分离出来的天然黄酮化合物，已被证明具有潜在的药理益处，如抗氧化、抗肿瘤和抗炎活性。本研究旨在研究铁死亡在I/R病理发生中的作用，并确定LCA是否可以抑制铁死亡以预防大鼠心肌I/R损伤。通过检测左室做功压力和三苯基四氮唑氯化物染色，检测LCA对心肌I/R损伤的影响。我们进行了Western博洛特分析、ELISA法和定量实时PCR来确定与铁死亡相关分子的水平。为了证明LCA在体外的心脏保护效应，我们将H9c2细胞和新生大鼠心肌细胞与铁死亡诱导剂(erastin、RSL3或Fe-SP)和LCA共同处理16和24小时。我们的体外研究表明，LCA增加了大鼠心脏I/R后的心肌收缩能力，减少了梗塞体积和与铁死亡相关的生物标志物。此外，LCA减少了铁死亡诱导剂引起的H9c2细胞和心肌细胞中的活性氧产生、脂质过氧化和与铁死亡相关的生物标志物的水平。LCA还减少了Fe-SP增加的核因子红细胞2相关因子2和血红素氧合酶1蛋白的水平。在本研究中，我们显示LCA诱导的心脏保护效应与调节铁死亡相关，并提供了预防或治疗心肌I/R损伤的可能新治疗策略。 版权所有 © 2023. Elsevier B.V. 出版。

Myocardial ischemia-reperfusion (I/R) injury triggers several cell death types, including apoptosis, autophagy, and ferroptosis. Licochalcone A (LCA), a natural flavonoid compound isolated from the root of Glycyrrhiza glabra, has been demonstrated to exert potential pharmacological benefits, such as antioxidant, antitumor, and anti-inflammatory activities. The present study aimed to investigate the involvement of ferroptosis in the pathogenesis of I/R and determine whether LCA can inhibit ferroptosis to prevent the myocardial I/R injury in rats. The effects of LCA on myocardial I/R injury were detected by examining the left ventricular-developed pressure and triphenyltetrazolium chloride staining. We conducted Western blotting analyses, ELISA assay, and quantitative real-time PCR to determine the levels of ferroptosis-related molecules. To demonstrate the cardioprotective effect of LCA in vitro, H9c2 and primary neonatal rat cardiomyocytes were co-treated with ferroptosis inducers (erastin, RSL3, or Fe-SP) and LCA for 16 and 24 h. Our ex vivo study showed that LCA increased the cardiac contractility, and reduced the infarct volume and ferroptosis-related biomarkers in rat hearts after I/R. Moreover, LCA reduced the levels of ferroptosis inducers-induced reactive oxygen species generation, lipid peroxidation, and ferroptosis-related biomarkers in cultured H9c2 cells and cardiomyocytes. LCA also reduced the Fe-SP-increased nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 protein levels in cultured cardiomyocytes. In the present study, we showed that the LCA-induced cardioprotective effects in attenuating the myocardial I/R injury were correlated with ferroptosis regulation, and provided a possible new therapeutic strategy for prevention or therapy of the myocardial I/R injury.Copyright © 2023. Published by Elsevier B.V.