Wine-derived phenolic metabolites and aroma compounds are effective at protecting neurons from nitrosative stress injury in vitro

Resumen del trabajo presentado al Wine Active Compounds (WAC), celebrado en Beaune (Francia) del 29 al 31 de marzo de 2017.

Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases, although the mechanisms implied behind this effect still remain unclear. Wine polyphenols are metabolized in the colon by gut microbiota, originating active and bioavailable metabolites. Recent evidences link wine components and interactions with different signalling routes, such as the mitogen-activated protein kinase (MAPK) pathway involved in neuroprotection. In the present study, a human dopaminergic neuronal cell line (SH-SY5Y) was used as a model of a neuroinflammation, to study the protective effects of wine-derived human phenolic metabolites and wine aroma compounds on neuronal survival, as well as their ability to interact with MAPK pathways (ERK1/2, JNK, p38) and pro-apoptotic signaling processes (STAT 1, caspase-3). SIN-1 (3-morpholinosydnonimine) has been used as a neuronal damage inductor. Gut-derived metabolites 3,4-dihydroxyphenylacetic (3,4DHPA), 3-hydroxyphenylacetic (3HPA) and salicylic ß-D-O-glucuronide at physiologically relevant concentrations (0.1-10 μM) resulted in increased cell viability (p <0.05) when compared to control. A significant decrease in MAPK p38 and ERK1/2 phosphorylation was also observed following pretreatment with 3,4DHPA, 3-(4-hydroxyphenyl) propionic acid (4HPP), 3HPA and 1,8-cineole; and with 3-(4-hydroxyphenyl) propionic (3HPP), 4HPP, 3HPA, linalool and 1,8-cineole, respectively. In a similar manner, a significant reduction in downstream pro-apoptotic caspase-3 activity was further observed following pre-incubation with 3HPP and linalool (p <0.05), counterbalancing the increase produced by SIN-1. Moreover, specific MEK, ERK1/2 and p38 inhibitors which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 levels. These results demonstrate for the first time that specific wine-derived human metabolites and aroma compounds are effective at protecting neurons from nitrosative stress injury by inhibiting neuronal MAPK ERK 1/2 and p38, as well as downstream caspase 3 activity.

Peer reviewed