Modulation of Neuronal Mitochondrial Injury by Gualou Guizhi Decoction in a Mouse Ischemia-Reperfusion Model.

Abstract

Background:

Objective: To investigate the effect and mechanism of Guilou Guizhi decoction (GLGZD) on CI/R injury.

Materials and methods: A middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was used to mimic ischemic stroke. GLGZD was administered by gavage, and the PI3K pathway inhibitor LY294002 was injected intraperitoneally. Neurological deficits, infarct volume, brain edema, and neuronal survival were assessed using mNSS scoring, TTC, HE, Nissl, and TUNEL staining. Mitochondrial function was evaluated by measuring membrane potential, ATP, and ROS levels. Western blot detected Cytc release, apoptosis markers, and PI3K/AKT/mTOR pathway activation.

Results: After GLGZD intervention, mNSS score, infarct area, and cerebral tissue water content were dramatically lowered in MCAO/R mice, histopathological damage and neuronal apoptosis in the cerebral cortex and CA1 region were significantly improved. Additionally, the mitochondrial membrane potential and ATP content were elevated, the level of ROS was lowered, the release of Cytc into the cytoplasm was reduced, and the level of neuronal apoptosis-related proteins. Furthermore, GLGZD therapy dramatically increased the phosphorylation status of PI3K/AKT/mTOR pathway molecules, and the pathway inhibitor LY294002 effectively reduced GLGZD's ameliorative effect on a variety of lesions in MCAO/R mice brain tissues.

Conclusion: GLGZD restores mitochondrial function via the PI3K/AKT/mTOR pathway to alleviate neuronal apoptosis in MCAO/R mice, suggesting its potential as a therapeutic agent for ischemic stroke.