Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Journal of Pharmacological Sciences

Fan-Hsiu Tsai³  Hao-Yuan Cheng³  Wei-Chu Li³  Yao-Tung Lin¹  Chia-Chang Hsieh²  Chi-Rei Wu³  Tsung-Chun Lu³  Wen-Huang Peng³  Ming-Tsuen Hsieh³ 

[1] China Medical University Hospital, School of Medicine, China Medical University, Taiwan;First Department of Internal Medicine, Kyorin University, School of Medicine, Japan;Graduate Institute of Chinese Pharmaceutical Sciences, College of Pharmacy, China Medical University, Taiwan

关键词: schizandrin;    glutamate;    cortical cell culture;    apoptosis;    neuroprotection;   

DOI  :  10.1254/jphs.FP0072394

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(58)Cited-By(21)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 μM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 μM) 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 μM. 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.

【 授权许可】

Unknown