Ferroptosis is closely associated with the pathophysiology of
myocardial ischemia.
Hydroxysafflor yellow A (HSYA), the main active ingredient in the Chinese herbal medicine safflower, exerts significant protective effects against
myocardial ischemia/
reperfusion injury (MI/RI). The aim of this study was to investigate the protective effects of HSYA against MI/RI and identify the putative underlying mechanisms. An in vivo model of acute MI/RI was established in C57 mice. Subsequently, the effects of HSYA on myocardial tissue injury were evaluated by histology. Lipid peroxidation and myocardial injury marker contents in myocardial tissue and serum and
iron contents in myocardial tissue were determined using biochemical assays. Mitochondrial damage was assessed using transmission electron microscopy. H9C2 cardiomyocytes were induced in vitro by
oxygen-
glucose deprivation/reoxygenation, and ferroptosis inducer
erastin was administered to detect ferroptosis-related indicators, oxidative-stress-related indicators, and expressions of ferroptosis-related
proteins and HIF-1α. In MI/RI model mice, HSYA reduced myocardial histopathological damage, ameliorated mitochondrial damage in myocardial cells, and decreased total cellular
iron and ferrous ion contents in myocardial tissue. HSYA increased the
protein levels of SLC7A11, HIF-1α, and GPX4 and mitigated
erastin- or HIF-1α
siRNA-induced damage in H9C2 cells. In summary, HSYA alleviated MI/RI by activating the HIF-1α/SLC7A11/GPX4 signaling pathway, thereby inhibiting ferroptosis.