Apple Procyanidins Suppress Amyloidβ-Protein Aggregation

Toshihiko Toda,Takuji Shirasawa,Tomomasa Kanda,Takahiko Shimizu,Motoyuki Tagashira,Tadahiro Sunagawa

doi:10.1155/2011/784698

Abstract

Procyanidins (PCs) are major components of the apple polyphenols (APs). We previously reported that treatment with PC extended the mean lifespan of Caenorhabditis elegans (Sunagawa et al., 2011). In order to estimate the neuroprotective effects of PC, we investigated the antiaggregative activity of PC on amyloid β-protein (Aβ) aggregation, which is a pathological hallmark of Alzheimer's disease. We herein report that PC significantly suppressed Aβ42 aggregation and dissociated Aβ42 aggregates in a dose-dependent manner, indicating that PC is a potent suppressor of Aβ aggregation. Furthermore, PC significantly inhibited Aβ42 neurotoxicity and stimulated proliferation in PC-12 cells. These results suggested that the PC and AP acted as neuroprotective factors against toxic Aβ aggregates.

Highlights

Polyphenols are comprised of several groups of compounds and belong to a family of plant secondary metabolites that widely accumulate in plants as well as fruits [1]
100 μg/mL apple polyphenols (APs) and 32.5 μg/mL PC completely abrogated amyloid β-protein (Aβ) aggregation throughout the incubation period (Figure 1(a), ns; not significant compared with 0 hour, P < 0.01), while monomer fraction (MN) resulted in a limited decrease in the Aβ aggregation (Figure 1(a))
Since 32.5 μg/mL PC corresponded to 100 μg/mL AP, this result suggests that PCs have approximately 2-fold the anti-Aβ aggregative ability compared to AP

Summary

Introduction

Polyphenols are comprised of several groups of compounds (e.g., anthocyanins, flavonols, and phenolic acids) and belong to a family of plant secondary metabolites that widely accumulate in plants as well as fruits [1]. We have revealed that apple PC showed antiallergy [15], antitumor [16], and antiobesity effects [17] in a rodent model and longevity effects on Caenorhabditis elegans [2]. In this context, PC might be a promising polyphenol that can prevent age-related diseases. AD is diagnosed by amyloid accumulation, which is observed as a deposition in the hippocampus and cerebral cortex, named a senile plaque, composed of amyloid β-proteins (Aβ) [18]. The protein forms strong aggregates themselves that are associated with neurotoxicity in vitro [19]. PCs suppress Aβ aggregation and cytotoxicity in vitro and strongly contribute to neuroprotection in AP

Materials and Methods

Results

Discussion