3-n-butylphthalide improves cerebral ischemia/reperfusion injury by regulating neuronal mitochondrial biogenesis via AMPK/PGC-1α signaling pathway.

Reperfusion therapy can lead to ischemia/reperfusion (I/R) injury in patients with ischemic stroke. The underlying mechanism of I/R injury is still unclear. At present, it is believed that mitochondrial quality control is the key to cerebral I/R injury. This study aimed to explore the protective effects of Race-3-n-Butylphthalide (NBP) on I/R injury and its underlying mechanism through the activation of the AMPK/PGC-1α pathway. The middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation/reoxygenation (OGD/R) model were used to evaluate NBP's effect on neuronal damage, oxidative stress, mitochondrial dysfunction, and mitochondrial biogenesis. Behavioral testing, including the rotarod and grip strength tests, was also performed to assess neurological function. Using both middle cerebral artery occlusion (MCAO) in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in primary neurons, we demonstrated that NBP enhances mitochondrial biogenesis via AMPK/PGC-1α activation, thereby mitigating neuronal I/R injury.