title: A tetramethylpyrazine piperazine derivate CXC137 prevents cell injury in SH-SY5Y cells and improves memory dysfunction of rats with vascular Dementia.
abstract: We investigated the effects of CXC137, a tetramethylpyrazine piperazine derivate, on cell damage induced by N-methyl-D-aspartate (NMDA) in human derived neuroblastoma cells (SH-SY5Y) and its effect on memory dysfunction of rats with vascular dementia. It was found that the presence of CXC137 increased SH-SY5Y cells viability by inhibition of cell apoptosis induced by NMDA. These effects of CXC137 were accompanied by increases of the antioxidant superoxide dismutase activity and the level of reduced glutathione, and a decrease of lipid peroxidation product, malondialdehyde. The presence of CXC137 also showed to produce strong inhibition of cellular lactate dehydrogenase leakage, cell apoptosis and intracellular calcium overload. In a vascular dementia rat model established by bilateral common carotid arteries occlusion, treatment with CXC137 from 2 to 35 day of post-operation significantly improves the motor performance, spatial learning and memory capability of rats in both the prehensile traction test and Morris water maze test, an effect that was companied by reductions of the animal glutamic acid levels and the degree of brain mitochondrial swelling. These results suggest that CXC137 can improve the memory dysfunction in dementia and thus has important therapeutic potential for the treatment of dementia.
authors.affiliation: Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, No. 44 Wen Hua Xi Road, Jinan, 250012, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Sun
authors.forename: Xin-Yong
authors.initials: XY
authors.lastname: Liu
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Shi
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Wang
authors.forename: Lu-Gang
authors.initials: LG
authors.lastname: Yu
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Guo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C000592135:CXC137; D010879:Piperazines; D011719:Pyrazines; D000255:Adenosine Triphosphate; D002118:Calcium