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) 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-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-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-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-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.

Anthocyanins: A Comprehensive Review of Their Chemical Properties and Health Effects on Cardiovascular and Neurodegenerative Diseases

“…This enhancement is confirmed by Western blot analysis of the memory-associated presynaptic and postsynaptic protein markers [ 239 , 240 ] and by behavioral tests. Anthocyanins improve learning and memory, which has been confirmed by the Morris water maze [ 240 , 243 , 244 , 245 , 252 , 253 , 254 , 260 , 264 , 265 , 266 ], Y-maze [ 240 , 255 ], novel object recognition [ 241 , 248 , 260 , 265 ] and passive avoidance [ 245 , 254 , 263 ] tests. Motor coordination is also improved by anthocyanins as confirmed by rotating rod test [ 244 ] and open-field [ 248 , 263 ] tests.…”

“…Additionally, anthocyanin-loaded polyethylene glycol-gold nanoparticles (PEG-AuNPs) regulate the p-PI3K/p-Akt/p-GSK3β pathway in the amyloid beta (Aβ)1–42 mouse model of Alzheimer’s disease. This regulation prevented the appearance of the tau protein during the hyperphosphorylation of serines 413 and 404 [ 240 ]. Blueberry attenuates radiation-induced oxidative stress in rats through attenuation of nicotinamide adenine dinucleotide phosphate as well as activation of Nrf2 [ 241 ].…”

Effect of Montmorency tart cherry juice on cognitive performance in older adults: a randomized controlled trial

“…Further, anthocyanin-rich supplements can inhibit tau hyperphosphorylation in the hippocampus and improve performance on cognitive behavioral tests as shown in mouse models of AD. 56 Our recent published studies 30,32 demonstrated that 12-week consumption of tart cherry juice lowered systolic BP by 4 mmHg and CRP by 25% as well as increased the plasma levels of DNA repair activity of OGG1. This supports the notion that the improvements in cognitive performance by tart cherry juice consumption may be due to its anti-inflammatory and anti-oxidative properties, and through a lowering of BP.…”

Wine Polyphenols and Neurodegenerative Diseases: An Update on the Molecular Mechanisms Underpinning Their Protective Effects

“…These observations indicate the ability of quercetin to decrease tau protein hyperphosphorylation and thereby to attenuate the associated neuropathology ( Figure 4) [79]. Anthocyanins were reported to activate the phosphorylation of anti-phosphorylated GSK3β at Ser 9, thereby possibly preventing GSK-3β-dependent tau hyperphosphorylation at Ser 413 and 404 [80]. GSPA is also able to decrease hyperphosphorylated tau deposition in APP/PS1 male heterozygous mice (Figure 4) [76].…”