Schizandrin protects primary cultures of rat cortical cells from glutamate-induced excitotoxicity

• Main Authors: Hao-Yuan Cheng, 鄭皓元
• Other Authors: 謝明村
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/93815571562853621048

博士 === 中國醫藥大學 === 中國藥學研究所 === 96 === The neuroprotective effect of schizandrin on the glutamate-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 μM glutamate for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin for 2 h significantly protected cortical neurons against glutamate-induced excitotoxicity. Schizandrin reduced apoptotic characteristics and the condensed nuclei evidenced by DAPI staining and DNA fragmentation in glutamate-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca2+ influx, and inhibited the subsequent overproduction of NO, ROS, cytochrome c and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased cellular level of GSH and inhibited the membrane lipid peroxidation (MDA). For Western blot, schizandrin increased the expression of Bcl-2 and Bcl-XL protein, whereas decreased the expression of Bax and Bak. Furthermore, schizandrin also decreased the expression of AIF and Nodo G protein. Schizandrin attenuated the protein levels changes of procaspase-9, caspase-9, caspase-3, cleaved PARP and endoplasmic reticulum stress of caspase-12. On the other hand, our results demonstrataed that the protective effect of schizandrin on glutamate-induced apoptosis was inhibited by the activation of phospho-ERK, phospho-JNK and phospho-P38. Taken together, these results indicated that regulation of the MAPK family, mitochondria mediated pathway and Bcl-2 family molecules, decreation of mitochrondrial cytochrome c release, and inactivation of caspase cascade may be the molecular mechanisms of schizandrin protected glutamate-induced apoptosis in the primary cultures of rat cortical cells.