Polyphenols in Alzheimer's Disease and in the Gut-Brain Axis.

V Prakash Reddy,Mark Obrenovich,Puspa Aryal,George Perry,Sara Robinson,Raheemat Rafiu

doi:10.3390/microorganisms8020199

Abstract

Polyphenolic antioxidants, including dietary plant lignans, modulate the gut–brain axis, which involves transformation of these polyphenolic compounds into physiologically active and neuroprotector compounds (called human lignans) through gut bacterial metabolism. These gut bacterial metabolites exert their neuroprotective effects in various neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and also have protective effects against other diseases, such as cardiovascular diseases, cancer, and diabetes. For example, enterolactone and enterodiol, the therapeutically relevant polyphenols, are formed as the secondary gut bacterial metabolites of lignans, the non-flavonoid polyphenolic compounds found in plant-based foods. These compounds are also acetylcholinesterase inhibitors, and thereby have potential applications as therapeutics in AD and other neurological diseases. Polyphenols are also advanced glycation end product (AGE) inhibitors (antiglycating agents), and thereby exert neuroprotective effects in cases of AD. Thus, gut bacterial metabolism of lignans and other dietary polyphenolic compounds results in the formation of neuroprotective polyphenols—some of which have enhanced blood–brain barrier permeability. It is hypothesized that gut bacterial metabolism-derived polyphenols, when combined with the nanoparticle-based blood–brain barrier (BBB)-targeted drug delivery, may prove to be effective therapeutics for various neurological disorders, including traumatic brain injury (TBI), AD, and PD. This mini-review addresses the role of polyphenolic compounds in the gut–brain axis, focusing on AD.

Highlights

Polyphenolic antioxidant compounds are mostly plant-derived phenolic compounds—some of which may exist as their ether or ester derivatives
Polyphenolic compounds are a diverse class of phenolic compounds that include flavanoids, such as epigallocatechin, epigallocatechin gallate, and catechin, and flavonoids, such as quercetin, fisetin, and luteolin, as pharmaceutically important compounds [1,2,3,4]
It is possible that the curcumin is transformed into more effective neuroprotective agents through the gut microbial metabolism

Summary

Introduction

Polyphenolic antioxidant compounds are mostly plant-derived phenolic compounds—some of which may exist as their ether (e.g., ferulic acid) or ester (e.g., epigallocatechin gallate) derivatives. Polyphenolic compounds are a diverse class of phenolic compounds that include flavanoids, such as epigallocatechin, epigallocatechin gallate, and catechin, and flavonoids, such as quercetin, fisetin, and luteolin, as pharmaceutically important compounds [1,2,3,4]. Other naturally occurring polyphenolic compounds include anthocyanidins, such as malvidin, and non-flavanoids/flavonoids, such as ferulic acid, gallic acid, caffeic acid, salicylic acid, and capsaicin (Figure 1). Polyphenolic phytochemicals occurring in various plant sources, including black soybeans, are effective in maintaining human health, especially in preventing cardiovascular diseases, neurological disorders, cancer, and diabetes, their therapeutic effect on the progress of the Alzheimer’s disease (AD) is debated, perhaps due to the irreversible neuronal damaMgiecroaotrgtahniesmlsa2t0e2r0,s8t,axgFeOsRoPfEAERDRE[V8I]E.W

Polyphenols as Antioxidants

Polyphenols in Alzheimer’s Disease

Oxidative Stress in the Formation of the Aβ Protein Aggregates

Polyphenols in the Modulation of the Signal Transduction Pathways

Findings

Polyphenols as Antiglycating Agents