Polyphenol metabolites and new molecules for attenuation of neuroinflammation

Dietary (poly)phenols are reported for their in vitro protective role in neuroinflammation. However, little is known if circulating metabolites, which reach the brain, retain this capacity. We previously showed that some of the (poly)phenols metabolites in circulation can cross the blood-brain barrier and be neuroprotective. We also tested for their anti-inflammatory capacity at physiological concentrations in microglia cells. One of the tested metabolites - pyrogallol-sulfate - was able to effectively reduce the levels of the inflammatory marker TNFα in a microglial model of inflammation stimulated with LPS. Our results suggest that these effects may be related with the NF-κB pathway, since we observed an increase of IκBα levels and a reduction in its phosphorylation levels. Novel synthetized derivatives of pyrogallol were also tested revealing a potentiation in the decrease of TNFα release. Moreover, using more physiological stimuli with TNFα and IFNγ in microglia cells, preliminary results suggest that the neuroprotective effect of pyrogallol-sulfate is maintained. This work highlights the potential of these human bioavailable (poly) phenol metabolites to mitigate the neuroinflammation process, a key process in the intricate complexity of neurodegenerative disorders.