Planta Med 2010; 76 - P579
DOI: 10.1055/s-0030-1264877

The neuroprotective effect of schizandrin on glutamate-induced neuronal excitotoxicity

S Lin 1, H Cheng 2, H Chen 3, M Lee 4, T Chou 5
  • 1National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan (R.O.C), 114 Taipei, Taiwan
  • 2Chung-Jen College of Nursing, Health Sciences and Management, No.1–10, Hubei Village, Dalin Township, Chiayi Country 622, Taiwan, ROC, 622 Chiayi County, Taiwan
  • 3Department of Safety, Health and Environmental Engineering, Mingchi University of Technology, Taipei, Taiwan, 84 Gungjuan Rd., Taishan, Taipei 24301, Taiwan, 243 Taipei, Taiwan
  • 4Department of Medical Research, Tungs Taichung MetroHarbor Hospital, Taichung, Taiwan, No.699, Sec.1, Chungchi Rd., Wuchi Township, Taichung County 435, Taiwan, 435 Taichung, Taiwan
  • 5National Defense medical center, graduate institute of life science, 114 No.161, Sec. 6, Minquan E. Rd., Neihu Dist., Taipei City 114, Taiwan (R.O.C.) Taipei, Taiwan

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.

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.

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