Galangin attenuated cerebral ischemia-reperfusion injury by inhibition of ferroptosis through activating the SLC7A11/GPX4 axis in gerbils

To evaluate the impact of galangin treatment on cerebral ischemia-reperfusion (I/R) injury in gerbils and to identify potential mechanisms of the protective effect of galangin on hippocampal neurons after I/R injury. A cerebral ischemia model using bilateral common carotid artery ligation in gerbils was established. The Morris water maze (MWM) test was used to evaluate the learning and memory ability of gerbils. The cell viability was evaluated with an MTT assay. The levels of lipid peroxide biomarkers were measured to estimate the injury due to lipid peroxide. The morphology was detected by electron micrography, immunofluorescence and Nissl staining. Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to measure the molecular characteristics. In the MWM, gerbils treated with galangin after I/R injury showed significant improvements in learning and memory. In addition, galangin treatment reduced the levels of lipid peroxide in the brains of gerbils that underwent I/R as well as reduced the amount of cell death and increased the expression of SLC7A11 and glutathione peroxidase 4 (GPX4). Furthermore, the expression of the marker of ferroptosis was decreased in galangin-treated gerbils, and the effect of galangin was weakened when SLC7A11 was knocked down. These results show that galangin can inhibit ferroptosis by enhancing the expressions of SLC7A11 and GPX4 as well as reduce neuronal cell death. Galangin inhibits ferroptosis through activation of the SLC7A11/GPX4 axis and has a protective effect on hippocampal neurons in gerbils after I/R. •Galangal can improve cognitive impairment in gerbils after I/R.•Galangal can reduce hippocampal neuronal injury in gerbils after I/R through antioxidant and anti-iron toxicity activities.•Galangin can inhibit neural ferroptosis by activating SLC7A11/GPX4 axis.