Department of Cardiology, Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
Department of Cardiovascular Medicine, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, People's Republic of China.
Drug Des Devel Ther. 2023 Aug 22;17:2495-2511. doi: 10.2147/DDDT.S409232. eCollection 2023.
Myocardial ischemic reperfusion injury (MIRI) is a crucial clinical problem globally. The molecular mechanisms of MIRI need to be fully explored to develop new therapeutic methods. Galangin (Gal), which is a natural flavonoid extracted from Alpinia Officinarum Hance and Propolis, possesses a wide range of pharmacological activities, but its effects on MIRI remain unclear. This study aimed to determine the pharmacological effects of Gal on MIRI.
C57BL/6 mice underwent reperfusion for 3 h after 45 min of ischemia, and neonatal rat cardiomyocytes (NRCs) subjected to hypoxia and reoxygenation (HR) were cultured as in vivo and in vitro models. Echocardiography and TTC-Evans Blue staining were performed to evaluate the myocardial injury. Transmission electron microscope and JC-1 staining were used to validate the mitochondrial function. Additionally, Western blot detected ferroptosis markers, including Gpx4, FTH, and xCT.
Gal treatment alleviated cardiac myofibril damage, reduced infarction size, improved cardiac function, and prevented mitochondrial injury in mice with MIRI. Gal significantly alleviated HR-induced cell death and mitigated mitochondrial membrane potential reduction in NRCs. Furthermore, Gal significantly inhibited ferroptosis by preventing iron overload and lipid peroxidation, as well as regulating Gpx4, FTH, and xCT expression levels. Moreover, Gal up-regulated nuclear transcriptive factor Nrf2 in HR-treated NRCs. Nrf2 inhibition by Brusatol abolished the protective effect of Gal against ferroptosis.
This study revealed that Gal alleviates myocardial ischemic reperfusion-induced ferroptosis by targeting Nrf2/Gpx4 signaling pathway.
心肌缺血再灌注损伤（MIRI）是一个全球性的重要临床问题。需要充分探索 MIRI 的分子机制，以开发新的治疗方法。姜黄素（Gal）是从益智和蜂胶中提取的天然类黄酮，具有广泛的药理活性，但它对 MIRI 的影响尚不清楚。本研究旨在探讨 Gal 对 MIRI 的药理作用。
C57BL/6 小鼠缺血 45 分钟后再灌注 3 小时，建立体内和体外模型，培养新生大鼠心肌细胞（NRCs）进行缺氧和复氧（HR）。采用超声心动图和 TTC-Evans Blue 染色评估心肌损伤。透射电镜和 JC-1 染色验证线粒体功能。Western blot 检测铁死亡标志物，包括 Gpx4、FTH 和 xCT。
Gal 治疗减轻了 MIRI 小鼠的心肌纤维损伤，减少了梗死面积，改善了心脏功能，防止了线粒体损伤。Gal 显著减轻了 HR 诱导的 NRC 细胞死亡和线粒体膜电位降低。此外，Gal 通过防止铁过载和脂质过氧化，以及调节 Gpx4、FTH 和 xCT 表达水平，显著抑制了铁死亡。此外，Gal 在 HR 处理的 NRCs 中上调了核转录因子 Nrf2。Brusatol 抑制 Nrf2 消除了 Gal 对铁死亡的保护作用。
本研究表明，Gal 通过靶向 Nrf2/Gpx4 信号通路缓解心肌缺血再灌注诱导的铁死亡。
