Role of intestinal microbiota in the generation of polyphenol‐derived phenolic acid mediated attenuation of Alzheimer's disease β‐amyloid oligomerization

Abstract

Scope Grape seed polyphenol extract (GSPE) is receiving increasing attention for its potential preventative and therapeutic roles in Alzheimer’s disease (AD) and other age-related neurodegenerative disorders. The intestinal microbiota is known to actively convert many dietary polyphenols, including GSPE, to phenolic acids. There is limited information on the bioavailability and bioactivity of GSPE-derived phenolic acid in the brain. Methods and Results We orally administered GSPE to rats and investigated the bioavailability of 12 phenolic acids known to be generated by microbiota metabolism of anthocyanidins. GSPE treatment significantly increased the content of 2 of the phenolic acids in the brain: 3-hydroxybenzoic acid (3-HBA) and 3-(3′-hydroxyphenyl) propionic acid (3-HPP), resulting in the brain accumulations of the two phenolic acids at μM concentrations. We also provided evidence that 3-HBA and 3-HPP potently interfere with the assembly of β-amyloid (Aβ) peptides into neurotoxic Aβ aggregates that play key roles in AD pathogenesis. Conclusion Our observation suggests important contribution of the intestinal microbiota to the protective activities of GSPE (as well as other polyphenol preparations) in AD. Outcomes from our studies support future preclinical and clinical investigations exploring the potential contributions of the intestinal microbiota in protecting against the onset/progression of AD and other neurodegenerative conditions.

Phenylethanoid Glycosides: Research Advances in Their Phytochemistry, Pharmacological Activity and Pharmacokinetics

“…For example, the hydrolyzing metabolites of 117 and 121, such as hydroxytyrosol (HT) and 3-hydroxyphenylpropionic acid (3-HPP), possessed antioxidant [116,117], neuroprotective [118][119][120], and anti-inflammatory activities [121,122]. Identification of 117's metabolites produced by human intestinal bacteria, biliary metabolites as well as urinary and fecal ones was reported.…”

Anthocyanin-rich plum juice reduces ambulatory blood pressure but not acute cognitive function in younger and older adults: a pilot crossover dose-timing study

“…An investigation on the bioavailability of anthocyanins observed an association between colon microbiota metabolism of anthocyanins and a significant increase in the content of generated polyphenols in the brain. There is a possibility that the peak levels observed at 6h is as a result of re-uptake of polyphenols in the colon [58,59]. For this reason, repeat cognitive tasks were administered 6 h post consumption of the plum juice for our study.…”

Surface rearrangement of adsorbed EGCG–mucin complexes on hydrophilic surfaces

“…Although such effects are prominent when tested in model systems, the complex interactions of polyphenols with dietary components and digestive systems result in very low levels of bioavailable polyphenol, giving rise to small, even physiologically insignificant effects from such scavenging, unless administered in extremely high doses. More recent data suggest that polyphenols are a unique class of substrates for colonic microflora [1,2]. Bioavailability of dietary polyphenols may not be a universal predictor of their physiological efficacy; other factors such as polyphenol ability to bind both mucins (which line the GIT) and dietary polysaccharides may play dominant roles.…”