Spatial metabolic analysis of the regulatory effects of DL-3-n-butylphthalide in a cerebral ischemia-reperfusion mouse model

DL-3-n-butylphthalide (NBP) exhibits promising pharmacological efficacy against ischemia-reperfusion injury, but its protective effects may involve many mechanisms that are yet to be fully understood. This study aimed to profile the metabolic alterations induced by NBP during the process of ischemia-reperfusion using spatial metabolomics. Our study found that NBP could significantly reduce the ischemic area and restore physical function by potentially modulating pathways of the citrate cycle, pyruvate metabolism, autophagy, and unsaturated fatty acid biosynthesis. During the process of ischemia-reperfusion, NBP played a therapeutic role in improving energy supply, decreasing autophagy, and improving unsaturated fatty acid biosynthesis. Subsequent studies confirmed improvements in relevant indices of mitochondrial morphology, autophagy, and ferroptosis after treatment with NBP. These findings shed light on novel mechanisms underlying the efficacy of NBP in treating cerebral ischemia/reperfusion injury associated with ischemic stroke.