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DOI: 10.1055/s-0030-1264877
The neuroprotective effect of schizandrin on glutamate-induced neuronal excitotoxicity
Glutamate (Glu) receptor-mediated toxicity is an important mechanism of neuronal damage in various pathologic conditions including ischemia, trauma, and neurodegeneration. The excitotoxic neuronal death induced by Glu has been shown to occur through both necrosis and apoptosis depending on Glu exposure. Fructus Schizandrae is widely used as a tonic in traditional Chinese medicine. Fructus Schizandrae contains dibenzocyclooctadiene lignans such as schizandrin. Schizandrin possesses many biological properties, including anti-inflammatory, antitumor, and a potentiating effect on glutathione mediated anti-oxidation. However, there has been less information concerning its protective function against Glu-induced neurotoxicity.
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Fig.1: Neuroprotective activities of Schizandrin against Gluinduced neurotoxicity and repression of cytochrome C release
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 cortical cells to Glu for 24h, cortical cell cultures exhibited apoptotic death. Pretreatment of the cortical cell cultures with schizandrin significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most robust at the concentration of 100µM. 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 NO, ROS, and preserved the mitochondrial membrane potential. Furthermore, schizandrin increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). Schizandrin attenuated the protein level changes of caspase-9, 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.
References: 1. Hsieh MT, Tsai ML, Peng WH, Wu CR. Effect of Fructus schizandrin on cycloheximide-induced amnesia in rats. Phytother Res. 1999;13:256–257.