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

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 that cyanidin 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.

• Authors: Nan Song, Ling Zhang, Wei Chen, Hua Zhu, Wei Deng, Yunlin Han, Jianguo Guo, Chuan Qin
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1862 Issue 9 Pg. 1786-800 (09 2016) ISSN: 0006-3002 [Print] Netherlands
• PMID: 27240542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• APP protein, human
• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Anthocyanins
• Glucosides
• PPAR gamma
• PSEN1 protein, human
• Peptide Fragments
• Presenilin-1
• Reactive Oxygen Species
• Recombinant Fusion Proteins
• amyloid beta-protein (25-35)
• cyanidin 3-O-glucopyranoside
• Glucose

Topics

• Alzheimer Disease (drug therapy, metabolism, psychology)
• Amyloid beta-Peptides (chemistry, genetics, metabolism)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Animals
• Anthocyanins (pharmacology)
• Apoptosis (drug effects)
• Brain (drug effects, metabolism)
• Cell Line
• Cognitive Dysfunction (drug therapy, metabolism, psychology)
• Disease Models, Animal
• Female
• Glucose (metabolism)
• Glucosides (pharmacology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Mutant Strains
• Mice, Transgenic
• Microscopy, Electron, Transmission
• Neurons (drug effects, metabolism, ultrastructure)
• PPAR gamma (agonists)
• Peptide Fragments (chemistry, genetics, metabolism)
• Presenilin-1 (genetics, metabolism)
• Protein Aggregation, Pathological (prevention & control)
• Reactive Oxygen Species (metabolism)
• Recombinant Fusion Proteins (genetics, metabolism)