In conclusion, our data revealed that AA9 improved brain infarct size and neurological deficits in the mice model of MCAO, and it also inhibits ischemic stroke‐induced neuronal damage, by rescuing iron deposition, ROS accumulation, and GPX4, Nrf2, HO‐1, HMGB1, and NF‐κB p65 expression. This evidence concerns the gene HMGB1 and ischemic stroke.