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

Research output: Contribution to journalArticlepeer-review


  • A Esteban-Fernández
  • J P E Spencer
  • D Gigorro Del Coso
  • M D González de Llano
  • B Bartolomé
  • M V Moreno-Arribas

Colleges, School and Institutes

External organisations

  • 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.
  • University of Reading
  • Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM , Madrid , Spain.


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.


Original languageEnglish
Pages (from-to)3
JournalFrontiers in Nutrition
Publication statusPublished - 14 Mar 2017


  • mitogen-activated protein kinase, neuroprotection, wine, polyphenols, gut phenolic metabolites, aroma compounds

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