Pine Bark Polyphenolic Extract Attenuates Amyloid-β and Tau Misfolding in a Model System of Alzheimer's Disease Neuropathology

Kenjiro Ono, Daisy Zhao, Qingli Wu, James Simon, Jun Wang, Aurelian Radu, Giulio Maria Pasinetti

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1597-1606
Number of pages10
JournalJournal of Alzheimer's Disease
Volume73
Issue number4
DOIs
StatePublished - 2020

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Keywords

  • Alzheimer's disease
  • amyloid β-peptide
  • polyphenols
  • tau

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