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Pine Bark Polyphenolic Extract Attenuates Amyloid-β and Tau Misfolding in a Model System of Alzheimer's Disease Neuropathology.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2020; Vol. 73 (4), pp. 1597-1606. - Publication Year :
- 2020
-
Abstract
- Plant-derived polyphenolic compounds possess diverse biological activities, including strong anti-oxidant, anti-inflammatory, anti-microbial, and anti-tumorigenic activities. There is a growing interest in the development of polyphenolic compounds for preventing and treating chronic and degenerative diseases, such as cardiovascular disorders, cancer, and neurological diseases including Alzheimer's disease (AD). Two neuropathological changes of AD are the appearance of neurofibrillary tangles containing tau and extracellular amyloid deposits containing amyloid-β protein (Aβ). Our laboratory and others have found that polyphenolic preparations rich in proanthocyanidins, such as grape seed extract, are capable of attenuating cognitive deterioration and reducing brain neuropathology in animal models of AD. Oligopin is a pine bark extract composed of low molecular weight proanthocyanidins oligomers (LMW-PAOs), including flavan-3-ol units such as catechin (C) and epicatechin (EC). Based on the ability of its various components to confer resilience to the onset of AD, we tested whether oligopin can specifically prevent or attenuate the progression of AD dementia preclinically. We also explored the underlying mechanism(s) through which oligopin may exert its biological activities. Oligopin inhibited oligomer formation of not only Aβ1-40 and Aβ1-42, but also tau in vitro. Our pharmacokinetics analysis of metabolite accumulation in vivo resulted in the identification of Me-EC-O-β-Glucuronide, Me-(±)-C-O-β-glucuronide, EC-O-β-glucuronide, and (±)-C-O-β-glucuronide in the plasma of mice. These metabolites are primarily methylated and glucuronidated C and EC conjugates. The studies conducted provide the necessary impetus to design future clinical trials with bioactive oligopin to prevent both prodromal and residual forms of AD.
- Subjects :
- Alzheimer Disease pathology
Amyloid beta-Peptides drug effects
Animals
Anthocyanins therapeutic use
Glucuronides metabolism
Male
Mice
Neurofibrillary Tangles pathology
Peptide Fragments drug effects
Plant Extracts pharmacokinetics
Plaque, Amyloid pathology
Polyphenols isolation & purification
Polyphenols pharmacokinetics
Prodromal Symptoms
Rats
Rats, Sprague-Dawley
Alzheimer Disease prevention & control
Amyloid beta-Peptides genetics
Plant Bark chemistry
Plant Extracts therapeutic use
Polyphenols therapeutic use
Proteostasis Deficiencies prevention & control
Vitis chemistry
tau Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 73
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 31958081
- Full Text :
- https://doi.org/10.3233/JAD-190543