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.

BackgroundAgeing can be simply defined as the process of becoming older, which is genetically determined but also environmentally modulated. With the continuous increase of life expectancy, quality of life during ageing has become one of the biggest challenges of developed countries. The quest for a healthy ageing has led to the extensive study of plant polyphenols with the aim to prevent age-associated deterioration and diseases, including neurodegenerative diseases. The world of polyphenols has fascinated researchers over the past decades, and in vitro, cell-based, animal and human studies have attempted to unravel the mechanisms behind dietary polyphenols neuroprotection.MethodsIn this review, we compiled some of the extensive and ever-growing research in the field, highlighting some of the most recent trends in the area.ResultsThe main findings regarding polypolyphenols neuroprotective potential performed using in vitro, cellular and animal studies, as well as human trials are covered in this review. Concepts like bioavailability, polyphenols biotransformation, transport of dietary polyphenols across barriers, including the blood-brain barrier, are here explored.ConclusionThe diversity and holistic properties of polypolyphenol present them as an attractive alternative for the treatment of multifactorial diseases, where a multitude of cellular pathways are disrupted. The underlying mechanisms of polypolyphenols for nutrition or therapeutic applications must be further consolidated, however there is strong evidence of their beneficial impact on brain function during ageing. Nevertheless, only the tip of the iceberg of nutritional and pharmacological potential of dietary polyphenols is hitherto understood and further research needs to be done to fill the gaps in pursuing a healthy ageing.

BBB transport of BDP and hBDP components reinforces the health benefits of a diet rich in polyphenols in neurodegenerative disorders. Our results suggest some novel pathways and genes that may be involved in the neuroprotective mechanism of the BDP polyphenol components.