Partridgeberry polyphenols protect primary cortical and hippocampal neurons against β-amyloid toxicity

Abstract

β-Amyloid (Aβ) deposition elicits a toxic effect on neurons and plays a crucial role in the etiology and/or progression of Alzheimer's disease (AD). Polyphenols found in fruits are endorsed for nutritional intervention in AD, since they are known to have extensive therapeutic properties apropos of brain health owing to their anti-oxidative effects against Aβ and neural reactive oxygen species (ROS). The present study was aimed to investigate the neuroprotective potential of polyphenols of partridgeberry (Vaccinium vitis-idaea L.) and elucidate the mechanism by which they confer protection against Aβ toxicity in rat primary neurons in vitro. The pre-treatment of rat primary cortical and hippocampal neurons with partridgeberry polyphenols (10–200μgmL−1) significantly attenuated Aβ-induced cell death and membrane damage. The flavan-3-ol- and flavonol-rich fractions of the partridgeberry exhibited the strongest ability to maintain cell viability (EC50 5.9μgmL−1) and prevent lactose dehydrogenase release (IC50 0.01μgmL−1) (P≤0.05). Similar to the maintenance of cellular viability, the flavan-3-ol- and flavonol-rich fractions also amplified the greatest activity of SOD and catalase among all polyphenol preparations exposed to neurons (P≤0.05). All four partridgeberry polyphenol preparations reduced the intracellular Aβ levels by 7–15 folds, and initiated Aβ clearance from neurons as compared to untreated cells (P≤0.05). Partridgeberry derived polyphenol preparations; especially the flavonol-rich fraction (IC50 97.1μgmL−1) significantly modulated the apoptotic targets and in vitro acetylcholinesterase activity (P≤0.05), indicating potential pharmacotherapy application in AD. Furthermore, the restoration of hyperactive caspases and Bcl2 family of apoptotic architects added to the neuroprotective candidacy of PPFs. These findings suggest that partridgeberry polyphenols, especially flavan-3-ol- and flavonol-rich fractions, could be of importance in prevention and/or treatment of AD.