Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer's disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid beta(1-42) (A beta(1-42)) oligomer to establish a cell model of AD in vitro. Schisandrin (2 mu g/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the A beta(1-42) oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the A beta(1-42) oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in A beta-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor gamma coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

Automated summary

The study demonstrated that Schisandrin significantly relieved the Aβ(1-42) oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity, and restricted the opening of mitochondrial permeability transition pore and release of cytochrome c. Additionally, alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes showed relief of defective energy metabolism in Aβ-treated neurons after Schisandrin treatment. Furthermore, elevated expression of peroxisome proliferator-activated receptor gamma coactivator along with promoted mitochondrial mass, and restoration of the imbalance in fusion and fission cycle were found in Schisandrin-treated cells.