Vincamine Alleviates Amyloid-β 25-35 Peptides-induced Cytotoxicity in PC12 Cells

Pharmacogn Mag. 2017 Jan-Mar;13(49):123-128. doi: 10.4103/0973-1296.196309.

Abstract

Objective: Vincamine is a plant alkaloid used clinically as a peripheral vasodilator that increases cerebral blood flow and oxygen and glucose utilization by neural tissue to combat the effect of aging. The main purpose of the present study is to investigate the influence of vincamine on amyloid-β 25-35 (Aβ25-35) induced cytotoxicity, to gain a better understanding of the neuroprotective effects of this clinically used anti-Alzheimer's disease drug.

Materials and methods: Oxidative stress was assessed by measuring malondialdehyde, glutathione, and superoxide dismutase (SOD) levels. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis detection was performed using an Annexin-V-FITC Apoptosis Detection Kit. The production of reactive oxygen species (ROS) was determined using an ROS Assay Kit. Western blot detection was carried out to detect the protein expression.

Results: Our studies showed that pretreatment with vincamine could reduce Aβ25-35 induced oxidative stress. Vincamine markedly inhibited cell apoptosis dose-dependently. More importantly, vincamine increased the phosphatidylinositol-3 kinase (PI3K)/Akt and Bcl-2 family protein ratios on preincubation with cells for 2 h.

Conclusion: Above observation led us to assume that one possible mechanism of vincamine protects Aβ25-35-induced cell death could be through upregulation of SOD and activation of the PI3K/Akt pathway.

Summary: Vincamine ameliorates amyloid-β 25-35 (Aβ25-35) peptides induced cytotoxicity in PC12 cellsVincamine reduces Aβ 25-35 peptides induced apoptosis of PC12 cellsVincamine activates the phosphatidylinositol-3 kinase/Akt pathwayVincamine up-regulates the superoxide dismutase. Abbreviation used: Aβ25-35: Amyloid-β 25-35; AD: Alzheimer's disease; BCA: Bicinchoninic acid; GSH: glutathione; PBS: Phosphate buffered solution; SDS: Sodium dodecylsulphate; SOD: Superoxide dismutase.