Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocytes.

Background: Ischemia/reperfusion (I/R) is associated with severe cellular damage and death. Ferroptosis, a new form of regulated cell death caused by the accumulation of iron-mediated lipid peroxidation, has been found in several diseases including I/R injury, which was reported to be suppressed by flavonoids. Baicalein (BAI) and luteolin (Lut) are flavonoids and were shown to reduce the myocardial I/R injury. BAI was found to suppress ferroptosis in cancer cells via reducing reactive oxygen species (ROS) generation. However, the anti-ferroptosis effect of Lut on ferroptosis has not been reported. This study aimed to investigate whether ferroptosis reduction contributes to the BAI- and Lut-protected cardiomyocytes.
Methods: This research used erastin, RSL3, and Fe-SP to induce ferroptosis. Cell viability was examined using MTT assay. Annexin V-FITC, CM-H ₂ DCFDA, and Phen Green SK diacetate (PGSK) fluorescent intensity were detected to analyze apoptotsis, ROS levels, and Fe ²⁺ concentrations, respectively. qPCR and Western blot analysis were conducted to detect the levels of mRNA and protein, respectively.
Results: Our data show that BAI and Lut protected cardiomyocytes against ferroptosis caused by ferroptosis inducers and I/R. Moreover, both BAI and Lut decreased ROS and malondialdehyde (MDA) generation and the protein levels of ferroptosis markers, and restored Glutathione peroxidase 4 (GPX4) protein levels in cardiomyocytes reduced by ferroptosis inducers. BAI and Lut reduced the I/R-induced myocardium infarction and decreased the levels of Acsl4 and Ptgs2 mRNA.
Conclusions: BAI and Lut could protect the cardiomyocytes against the I/R-induced ferroptosis via suppressing accumulation of ROS and MDA.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier B.V. All rights reserved.)