Division of Experimental Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan.
Department of Physiology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Eur J Pharmacol. 2023 Oct 15;957:176031. doi: 10.1016/j.ejphar.2023.176031. Epub 2023 Sep 1.
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.
心肌缺血再灌注（I/R）损伤触发多种细胞死亡类型，包括细胞凋亡、自噬和铁死亡。甘草查尔酮 A（LCA）是从甘草根中分离得到的一种天然黄酮类化合物，已被证明具有潜在的药理作用，如抗氧化、抗肿瘤和抗炎活性。本研究旨在探讨铁死亡在 I/R 发病机制中的作用，并确定 LCA 是否可以抑制铁死亡来预防大鼠心肌 I/R 损伤。通过检测左心室发展压和氯化三苯基四氮唑染色来检测 LCA 对心肌 I/R 损伤的影响。我们进行了 Western blot 分析、ELISA 测定和定量实时 PCR 来确定铁死亡相关分子的水平。为了证明 LCA 在体外的心脏保护作用，将 H9c2 和原代新生大鼠心肌细胞与铁死亡诱导剂（erastin、RSL3 或 Fe-SP）和 LCA 共同孵育 16 和 24 小时。我们的离体研究表明，LCA 增加了心脏的收缩力，减少了大鼠心脏 I/R 后的梗塞面积和铁死亡相关生物标志物。此外，LCA 降低了铁死亡诱导剂诱导的活性氧生成、脂质过氧化和铁死亡相关生物标志物在培养的 H9c2 细胞和心肌细胞中的水平。LCA 还降低了 Fe-SP 增加的培养心肌细胞中核因子红细胞 2 相关因子 2 和血红素加氧酶-1 蛋白水平。在本研究中，我们表明，LCA 诱导的心脏保护作用减轻心肌 I/R 损伤与铁死亡调节有关，并为预防或治疗心肌 I/R 损伤提供了一种新的可能治疗策略。
