title: Neuroprotective Effects of Selected Microbial-Derived Phenolic Metabolites and Aroma Compounds from Wine in Human SH-SY5Y Neuroblastoma Cells and Their Putative Mechanisms of Action.
abstract: Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases. This study investigates the molecular mechanisms underlying the protective effects of wine-derived phenolic and aroma compounds in a neuroinflammation model based on SIN-1 stress-induced injury in SH-SY5Y neuroblastoma cells. Cell pretreatment with microbial metabolites found in blood after wine consumption, 3,4-dihydroxyphenylacetic (3,4-DHPA), 3-hydroxyphenylacetic acids and salicylic β-d-O-glucuronide, at physiologically concentrations (0.1-10 μM) resulted in increased cell viability versus SIN-1 control group (p< 0.05). Results also showed significant decreases in mitogen-activated protein kinase (MAPK) p38 and ERK1/2 activation as well as in downstream pro-apoptotic caspase-3 activity by some of the studied compounds. Moreover, pretreatment with p38, MEK, and ERK1/2-specific inhibitors, which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 activity levels. Overall, these results contribute with new evidences related to the neuroprotective actions of wine, pointing out that wine-derived human metabolites and aroma compounds may be effective at protecting neuroblastoma cells from nitrosative stress injury by inhibiting neuronal MAPK p38 and ERK1/2, as well as downstream caspase 3 activity.
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, Madrid, Spain; Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
authors.forename: A
authors.initials: A
authors.lastname: Esteban-Fernández
authors.affiliation: Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign , Champaign, IL , USA.
authors.forename: C
authors.initials: C
authors.lastname: Rendeiro
authors.affiliation: Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading , Reading , UK.
authors.forename: J P E
authors.initials: JP
authors.lastname: Spencer
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM , Madrid , Spain.
authors.forename: D Gigorro
authors.initials: DG
authors.lastname: Del Coso
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM , Madrid , Spain.
authors.forename: M D González
authors.initials: MD
authors.lastname: de Llano
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM , Madrid , Spain.
authors.forename: B
authors.initials: B
authors.lastname: Bartolomé
authors.affiliation: Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM , Madrid , Spain.
authors.forename: M V
authors.initials: MV
authors.lastname: Moreno-Arribas
keywords: aroma compounds; gut phenolic metabolites; mitogen-activated protein kinase; neuroprotection; polyphenols; wine