Polyphenols journey through blood-brain barrier towards neuronal protection

Abstract

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to influence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for differential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and inflammatory injuries and this attenuation of neuroinflammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated inflammation and exert neuroprotective effects, with potential for alleviation of neurodegenerative diseases.

Hempseed Lignanamides Rich-Fraction: Chemical Investigation and Cytotoxicity towards U-87 Glioblastoma Cells

“…In this context, the ability of LnHS (and pure compounds therefrom) to cross the blood brain barrier (BBB) is aimed to be promptly pursued. This is in line with several recent evidences which highlight the ability of dietary polyphenols, and their known physiologically relevant metabolites, to enter the brain endothelium, cross the BBB and to impact brain health and cognition [61][62][63]. The BBB-crossing feature in phenylamides and lignanamides could be improved by the intrinsic amide function occurrence.…”

Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration

“…Microbial metabolites derived from dietary lignans, a class of polyphenols, like equol and enterolactone, passively cross both the gut and BBB barriers and show protective ability against inflammation in microglia [128]. A recent study demonstrates that microbial polyphenol metabolites could be transported across the BBB endothelium [129]. In vitro experiments showed that some polyphenols' metabolites cross BBB by transmembrane diffusion and their lipophilicity can determine greater or minor uptake [130].…”

Chronic Polyphenon-60 or Catechin Treatments Increase Brain Monoamines Syntheses and Hippocampal SIRT1 LEVELS Improving Cognition in Aged Rats

“…Oxidative stress environment is believed to be one of the main factors of this age-associated brain disfunction, induced by reduced endogenous antioxidant levels and increased reactive oxygen species (ROS) production, linked to a chronic low-grade neuroinflammatory status [2][3][4]. Dietary antioxidants, with special relevance of polyphenols due to their availability in the diet, have been shown to limit some effects of aging, particularly brain aging, due to their capacity to cross the blood-brain barrier [5][6][7]. Among polyphenol-rich products, the green tea extracts (made from Camellia sinensis leaves) have drawn attention due to its large consumption worldwide as an infusion.…”