Panaxydol and panaxynol protect cultured cortical neurons against Abeta25-35-induced toxicity.
Amyloid beta protein (Abeta), the central constituent of senile plaques in Alzheimer's disease (AD), is known to exert toxic effects on cultured neurons. In the present study, the protective effect of panaxydol (PND) and panaxynol (PNN) on Abeta25-35-induced neuronal apoptosis and potential mechanisms were investigated in primary cultured rat cortical neurons. Pretreatment of the cells with PND or PNN prior to 10 microM Abeta25-35 exposure resulted significantly in elevation of cell survival determined by MTT assay, TUNEL/Hoechst staining and western blot. Furthermore, a marked increase in calcium influx and intracellular free radical generation was found after Abeta25-35 exposure, which could be almost completely reversed by pretreatment of PND or PNN. PND and PNN could also alleviate Abeta25-35-induced early-stage neuronal degeneration. These results indicated that inhibition of calcium influx and free radical generation is a mechanism of the anti-apoptotic action of PND and PNN. Since Abeta plays critical roles in the pathogenesis of AD, these findings raise the possibility that PND and PNN reduce neurodegeneration in AD.
Nie
Bao-Ming
BM
Department of Pharmacy, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
Jiang
Xiao-Yan
XY
Cai
Jin-Xian
JX
Fu
Sai-Li
SL
Yang
Li-Min
LM
Lin
Lin
L
Hang
Qin
Q
Lu
Pei-Lua
PL
Lu
Yang
Y
D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D053280:Diynes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005233:Fatty Alcohols / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling / Q000379:methods; D018613:Microscopy, Confocal / Q000379:methods; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D053280:Diynes; D005233:Fatty Alcohols; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D013778:Tetrazolium Salts; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; C018541:falcarinol; C055778:panaxydol; C022616:thiazolyl blue; D002118:Calcium