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Cyanidin 3-O-β-glucopyranoside activates peroxisome proliferator-activated receptor-γ and alleviates cognitive impairment in the APP(swe)PS1(ΔE9) mouse model

2017年12月21日 来源:

Song NZhang LChen WZhu HDeng WHan YGuo JQin C.

Abstract

       Alzheimer's disease (AD) is currently one of the most common neurodegenerative disorders worldwide. To date, no cure has been developed for AD, and some disease-modifying treatments show side effects and low efficacy. Increasing evidence shows thatcyanidin 3-O-β-glucopyranoside (Cy3G), which is naturally derived from many plants, may provide protection against neurodegenerative diseases including AD; however, its exact role is still unclear. Therefore, we investigated the mechanisms of the effects of Cy3G on beta-amyloid 25-35 (Aβ25-35)-induced SH-SY5Y cell injury and cognitive impairment in the APP(swe)/PS1(ΔE9) (PAP) mouse model of AD. Furthermore, we aimed to determine the molecular target initiated by Cy3G. The data indicated that Cy3G-mediated neuroprotection involved the inhibition of Aβ25-35 binding to the cell surface and spontaneous aggregation of Aβ25-35 fibrils at the molecular level. Furthermore, in an in vitro study, Aβ25-35-mediated cytotoxicity, which was caused by inducing apoptotic cell death and ROS formation, was also ameliorated by Cy3G intervention. In addition, upregulation of peroxisome proliferator-activated receptor-γ (PPARγ) protein involved in glucose/lipid metabolism by Cy3G treatment verified that the initiated molecule was Cy3G. In an in vivo study, Cy3G was shown to alleviate cognitive impairment, improve cerebral glucose uptake and decrease fasting blood glucose levels. In conclusion, Cy3G ameliorates amyloid β peptide-induced injury both in vitro and in vivo through the PPARγ pathway. Thus, Cy3G has a good safety profile as a potential natural PPARγ agonist and may be used as an ideal alternative to traditional disease-modifying treatments against AD.

全文下载:http://linkinghub.elsevier.com/retrieve/pii/S0925-4439(16)30133-8