Icariin inhibits hypoxia/reoxygenation‐induced ferroptosis of cardiomyocytes via regulation of the Nrf2/HO‐1 signaling pathway
Xiujuan Liu, Yanfei Lv, Wen‐Zhu Cui, Yan Li, Yang Liu, Yitao Xue, Feng Dong
Abstract
Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia. Ferroptosis is a crucial event in myocardial injury, and icariin (ICA) exerts protective effects against myocardial injury. Here, we investigated the protective mechanism of ICA in hypoxia/reoxygenation (H/R)‐induced ferroptosis of cardiomyocytes. H9C2 cells were subjected to H/R induction. The content of lactate dehydrogenase and the levels of oxidative stress and intracellular ferrous ion Fe 2+ were measured. The levels of ferroptosis markers (ACSL4 and GPX4) were detected. H/R‐induced H9C2 cells were cultured with ICA in the presence or absence of ferroptosis inducer (erastin). Znpp (an HO‐1 inhibitor) was added to ICA‐treated H/R cells to verify the role of the Nrf2/HO‐1 pathway. H/R‐induced H9C2 cells showed reduced viability, enhanced oxidative stress and lactate dehydrogenase content, increased levels of Fe 2+ and ACSL4, and decreased levels of GPX4. ICA inhibited H/R‐induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO‐1 in H/R‐induced H9C2 cells was reduced, whereas ICA treatment reversed this trend. Inhibition of the Nrf2/HO‐1 pathway reversed the protective effect of ICA on H/R‐induced ferroptosis. Collectively, our results suggest that ICA attenuates H/R‐induced ferroptosis of cardiomyocytes by activating the Nrf2/HO‐1 signaling pathway.