cytochrome-c-t and schizandrin

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.. Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons.. In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1-42 (Aβ1-42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1-42 oligomer-treated neurons.. Our findings indicated that schisandrin significantly alleviated the Aβ1-42 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 Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ 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.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Animals, Newborn; Cyclooctanes; Cytochromes c; Energy Metabolism; Hippocampus; Lignans; Membrane Potential, Mitochondrial; Mitochondria; Mitochondrial Dynamics; Models, Biological; Neurons; Neuroprotective Agents; Organelle Biogenesis; Peptide Fragments; Polycyclic Compounds; Primary Cell Culture; Rats, Sprague-Dawley

The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 microM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 microM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 microM. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

Topics: Animals; Apoptosis; Calcium; Caspases; Cells, Cultured; Cerebral Cortex; Cyclooctanes; Cytochromes c; Dizocilpine Maleate; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Glutamic Acid; Glutathione; Lignans; Lipid Peroxidation; Membrane Potential, Mitochondrial; Mitochondria; Neurons; Neuroprotective Agents; Nitric Oxide; Oxidative Stress; Poly(ADP-ribose) Polymerases; Polycyclic Compounds; Rats; Reactive Oxygen Species