大黄素通过抑制铁死亡缓解阿霉素所致的心脏毒性。
Aloe-emodin alleviates doxorubicin-induced cardiotoxicity via inhibition of ferroptosis.
机构信息
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu, 730000, China; School of Chemistry and Chemical Engineering, Nanjing University of Science & Technology, Nanjing, Jiangsu, 210094, China.
出版信息
Free Radic Biol Med. 2023 Sep;206:13-21. doi: 10.1016/j.freeradbiomed.2023.06.025. Epub 2023 Jun 25.
Aloe-emodin (AE), a novel ferroptosis inhibitor, alleviates the doxorubicin (DOX)-induced cardiotoxicity in H9c2 rat cardiomyocytes. The inhibition of ferroptosis and the protective effect against cardiotoxicity were evaluated via MTT assay in H9c2 cells. The molecular mechanism of action (MOA) of nuclear factor erythroid 2-related factor 2 (Nrf2) activation, including transactivation of multiple downstream cytoprotective genes, were further assessed by Western blot, luciferase reporter assay and qRT-PCR analyses. Fluorescent imaging was performed to detect the change of intracellular reactive oxygen species, mitochondrial membrane potential and lipid peroxidation. In addition, an infrared spectroscopy was employed to detect the AE-Fe (II) complex. AE, alleviates oxidative stress in DOX-induced H9c2 cells by activating Nrf2 and increasing the expression of Nrf2 downstream antioxidant genes, SLC7A11 and GPX4. Furthermore, AE complexes bivalent iron and regulates the intracellular iron-related genes. In conclusion, the discovery of AE as a novel ferroptosis inhibitor and its MOA provides a new perspective for further exploration of cardio-protective agents in cancer patients during chemotherapy.
大黄素（AE）是一种新型的铁死亡抑制剂，可减轻阿霉素（DOX）诱导的 H9c2 大鼠心肌细胞的心脏毒性。通过 MTT 法在 H9c2 细胞中评估铁死亡抑制作用和心脏毒性保护作用。通过 Western blot、荧光素酶报告基因检测和 qRT-PCR 分析进一步评估核因子红细胞 2 相关因子 2（Nrf2）激活的作用机制（MOA），包括多个下游细胞保护基因的转录激活。通过荧光成像检测细胞内活性氧、线粒体膜电位和脂质过氧化的变化。此外，还采用红外光谱法检测 AE-Fe（II）配合物。AE 通过激活 Nrf2 并增加 Nrf2 下游抗氧化基因 SLC7A11 和 GPX4 的表达，减轻 DOX 诱导的 H9c2 细胞中的氧化应激。此外，AE 复合物调节二价铁和细胞内铁相关基因。总之，发现 AE 作为一种新型的铁死亡抑制剂及其 MOA 为进一步探索化疗期间癌症患者心脏保护剂提供了新的视角。
Zotero 插件