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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.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Sep; Vol. 1862 (9), pp. 1786-800. Date of Electronic Publication: 2016 May 27. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Alzheimer Disease drug therapy
Alzheimer Disease metabolism
Alzheimer Disease psychology
Amyloid beta-Peptides chemistry
Amyloid beta-Peptides genetics
Amyloid beta-Peptides metabolism
Amyloid beta-Protein Precursor genetics
Amyloid beta-Protein Precursor metabolism
Animals
Apoptosis drug effects
Brain drug effects
Brain metabolism
Cell Line
Cognitive Dysfunction metabolism
Cognitive Dysfunction psychology
Disease Models, Animal
Female
Glucose metabolism
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Mice, Transgenic
Microscopy, Electron, Transmission
Neurons drug effects
Neurons metabolism
Neurons ultrastructure
Peptide Fragments chemistry
Peptide Fragments genetics
Peptide Fragments metabolism
Presenilin-1 genetics
Presenilin-1 metabolism
Protein Aggregation, Pathological prevention & control
Reactive Oxygen Species metabolism
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Anthocyanins pharmacology
Cognitive Dysfunction drug therapy
Glucosides pharmacology
PPAR gamma agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1862
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 27240542
- Full Text :
- https://doi.org/10.1016/j.bbadis.2016.05.016