Anthocyanin-Loaded PEG-Gold Nanoparticles Enhanced the Neuroprotection of Anthocyanins in an Aβ1-42 Mouse Model of Alzheimer's Disease

Abstract

Nanomedicine is an emerging research area. In this study, we investigated the neuroprotective efficacy of anthocyanin-loaded polyethylene glycol-gold nanoparticles (PEG-AuNPs) for enhancing the neuroprotective efficacy of anthocyanins in an amyloid beta (Aβ)_1-42 mouse model of Alzheimer's disease. We observed that both anthocyanin-loaded PEG-AuNPs and anthocyanins treatment (12 μg/g/day for 14 days) ameliorated memory impairments in the Aβ_1-42-injected mice. However, the anthocyanin-loaded PEG-AuNPs were more effective than free anthocyanins. Anthocyanin-loaded PEG-AuNPs protected pre- and post-synaptic proteins from Aβ_1-42-induced synaptic dysfunction. Interestingly, the anthocyanin-loaded PEG-AuNPs also regulated the p-PI3K/p-Akt/p-GSK3β pathway and, as a result, prevented the hyperphosphorylation of tau protein at serines 413 and 404 in the Aβ_1-42-injected mice. Western blot results of cytochrome c, Bax/Bcl2, caspases and poly (ADP-ribose) polymerase-1 expression levels, and immunohistochemical Nissl and Fluoro-Jade B staining also indicated that the anthocyanin-loaded PEG-AuNPs inhibited apoptosis and neurodegeneration in the Aβ_1-42-injected mice. Our results suggest that the conjugation of dietary polyphenolic compounds with gold nanoparticles, such as anthocyanin-loaded PEG-AuNPs, is a novel approach that may represent an important and promising nanomedicine strategy to prevent age-associated neurodegenerative diseases.

Keywords: Alzheimer’s disease; Anthocyanin-PEG-gold nanoparticles; Nanomedicine; Neurodegeneration; Synaptic dysfunction.