Vinpocetine attenuates the metabolic dysfunction induced by amyloid beta-peptides in PC12 cells

The cytoprotective effect of vinpocetine [14-ethoxycarbonyl-(3 alpha ,16 al pha -ethyl)-14,15-eburnamine] was investigated on PC12 cells treated with t he amyloid beta -peptides (A beta) for 24 hours. Vinpocetine was shown to p rotect cells from the inhibition in redox status induced by exposure to A b eta (25-35) and A beta (1-40), the maximal protection being achieved at a v inpocetine concentration of 40 muM. At this concentration, vinpocetine bloc ked the inhibition of the mitochondrial respiratory chain complexes II-III and IV and completely abolished the depletion of pyruvate levels induced by toxic concentrations of A beta peptides. Furthermore, the accumulation of ROS in cells exposed to A beta (25-35) and A beta (1-40)evaluated using the fluorescent probe 2',7'-dichlorofluorescin (DCF), was reduced in the prese nce of 40 muM vinpocetine. Taken together, the data presented herein demons trate that vinpocetine protects cells from A beta toxicity, preventing the generation of oxidative stress due to the excessive accumulation of ROS. Th is study suggests that vinpocetine can exert neuroprotective properties whi ch might be of importance and contribute to its clinical efficacy in the tr eatment of Alzheimer's disease or other neurodegenerative disorders in whic h oxidative stress is involved.