Polyphenols journey through blood-brain barrier towards neuronal protection.
I FigueiraGonçalo GarciaR C PimpãoA P TerrassoI CostaAndreia F AlmeidaL TavaresT F PaisP PintoM R VenturaA FilipeG J McDougallD StewartK S KimI PalmelaD BritesMaria Alexandra BritoCatarina BritoC N SantosPublished in: Scientific reports (2017)
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.
Keyphrases
- blood brain barrier
- cerebral ischemia
- endothelial cells
- oxidative stress
- induced apoptosis
- human health
- signaling pathway
- traumatic brain injury
- physical activity
- lps induced
- white matter
- risk assessment
- inflammatory response
- weight loss
- brain injury
- subarachnoid hemorrhage
- immune response
- multiple sclerosis
- ulcerative colitis
- spinal cord injury
- spinal cord
- resting state
- nuclear factor
- molecular dynamics simulations