Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
Department of medicine, JingGangshan University, Ji'an, Jiangxi province, China.
Mol Cell Biochem. 2024 Apr;479(4):869-880. doi: 10.1007/s11010-023-04769-1. Epub 2023 May 24.
Eupatilin is a pharmacologically active flavonoid with a variety of biological activities, such as anticancer, anti-inflammatory, antioxidant, neuroprotective, anti-allergic and cardioprotective effects. However, whether eupatilin has protective effects on doxorubicin-induced cardiotoxicity remains unknown. Thus, this study aimed to investigate the role of eupatilin in doxorubicin-induced cardiotoxicity. Mice were exposed to a single dose of doxorubicin (15 mg/kg) to generate doxorubicin-induced cardiotoxicity or normal saline as a control. To explore the protective effects, mice were intraperitoneally injected with eupatilin daily for 7 days. Then, we examined the changes in cardiac function, inflammation, apoptosis, and oxidative stress to evaluate the effects of eupatilin on doxorubicin-induced cardiotoxicity. Additionally, RNA-seq analysis was introduced to explore the potential molecular mechanisms. Eupatilin ameliorated doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and cardiomyocyte apoptosis and ameliorated doxorubicin-induced cardiac dysfunction. Mechanistically, eupatilin activated the PI3K-AKT signaling pathway, as evidenced by RNA-seq analysis and Western blot analysis. This study provides the first evidence that eupatilin ameliorates doxorubicin-induced cardiotoxicity by attenuating inflammation, oxidative stress, and apoptosis. Pharmacotherapy with eupatilin provides a novel therapeutic regimen for doxorubicin-induced cardiotoxicity.
芹菜素是一种具有多种生物活性的药理活性类黄酮，具有抗癌、抗炎、抗氧化、神经保护、抗过敏和心脏保护作用。然而，芹菜素是否对阿霉素诱导的心肌毒性具有保护作用尚不清楚。因此，本研究旨在探讨芹菜素在阿霉素诱导的心肌毒性中的作用。通过单次给予阿霉素（15mg/kg）使小鼠产生阿霉素诱导的心肌毒性，或给予生理盐水作为对照。为了探讨保护作用，小鼠每天腹腔注射芹菜素 7 天。然后，我们检测了心脏功能、炎症、细胞凋亡和氧化应激的变化，以评估芹菜素对阿霉素诱导的心肌毒性的影响。此外，还进行了 RNA-seq 分析以探讨潜在的分子机制。芹菜素通过减轻炎症、氧化应激和心肌细胞凋亡改善了阿霉素诱导的心肌毒性，并改善了阿霉素诱导的心脏功能障碍。机制上，RNA-seq 分析和 Western blot 分析表明，芹菜素激活了 PI3K-AKT 信号通路。本研究首次提供了芹菜素通过减轻炎症、氧化应激和细胞凋亡来改善阿霉素诱导的心肌毒性的证据。芹菜素的药物治疗为阿霉素诱导的心肌毒性提供了一种新的治疗方案。
