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.