Pine Bark Polyphenolic Extract Attenuates Amyloid-β and Tau Misfolding in a Model System of Alzheimer’s Disease Neuropathology¹

Article type: Research Article

Authors: Ono, Kenjiro^a | Zhao, Daisy^b | Wu, Qingli^b | Simon, James^b | Wang, Jun^c | Radu, Aurelian^d | Pasinetti, Giulio Maria^{c; e; *}

Affiliations: [a] Department of Internal Medicine, Division of Neurology, Showa University School of Medicine, Tokyo, Japan | [b] New Use Agriculture and Natural Plant Products Program, Department of Plant Biology, Rutgers University, New Brunswick, NJ, USA | [c] Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [d] Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [e] Geriatric Research, Education and Clinical Center, James J. Peters Veterans Affairs Medical, Center, Bronx, NY, USA

Correspondence: [*] Correspondence to: Giulio Maria Pasinetti, MD, PhD, Department of Neurology, The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, USA. Tel.: +1 212 241 7938; E-mail: [email protected].

Note: [1] This article received a correction notice (Erratum) with the reference: 10.3233/JAD-209007, available at https://content.iospress.com/articles/journal-of-alzheimers-disease/jad209007.

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.

Keywords: Alzheimer’s disease, amyloid β-peptide, polyphenols, tau

DOI: 10.3233/JAD-190543

Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1597-1606, 2020