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A Polyphenol-Enriched Supplement Exerts Potent Epigenetic-Protective Activity in a Cell-Based Model of Brain Ischemia

Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
European Institute of Nutritional Medicine, E.I.Nu.M., Viale Liegi 44, 00198 Rome, Italy
Author to whom correspondence should be addressed.
These authors have contributed equally to this study.
Nutrients 2019, 11(2), 345;
Received: 12 December 2018 / Revised: 27 January 2019 / Accepted: 3 February 2019 / Published: 6 February 2019
PDF [1553 KB, uploaded 18 February 2019]


Bioactive components, due in part to their epigenetic properties, are beneficial for preventing several human diseases including cerebrovascular pathologies. However, no clear demonstration supports the idea that these molecules still conserve their epigenetic effects when acting at very low concentrations reproducing the brain levels achieved after oral administration of a micronutrient supplement. In the present study, we used a cellular model of brain ischemia to investigate the neuroprotective and epigenetic activities of a commercially available micronutrient mixture (polyphenol-enriched micronutrient mixture, PMM) enriched in polyphenols ((-)-epigallocatechin-3-gallate, quercetin, resveratrol), α-lipoic acid, vitamins, amino acids and other micronutrients. Mimicking the suggested dietary supplementation, primary cultures of mouse cortical neurons were pre-treated with PMM and then subjected to oxygen glucose deprivation (OGD). Pre-treatment with PMM amounts to provide bioactive components in the medium in the nanomolar range potently prevented neuronal cell death. The protection was associated with the deacetylation of the lysin 310 (K310) on NF-κB/RelA as well as the deacetylation of H3 histones at the promoter of Bim, a pro-apoptotic target of ac-RelA(K310) in brain ischemia. Epigenetic regulators known to shape the acetylation state of ac-RelA(K310) moiety are the histone acetyl transferase CBP/p300 and the class III histone deacetylase sirtuin-1. In view of that evidence, the protection we here report unveils the efficacy of bioactive components endowed with either inhibitory activity on CBP/p300 or stimulating activity on the AMP-activated protein kinase–sirtuin 1 pathway. Our results support a potential synergistic effect of micronutrients in the PMM, suggesting that the intake of a polyphenol-based micronutrient mixture can reduce neuronal vulnerability to stressful conditions at concentrations compatible with the predicted brain levels reached by a single constituent after an oral dose of PMM. View Full-Text
Keywords: brain ischemia; OGD; NF-κB/RelA; HATs; HDACs; polyphenols; green tea; resveratrol brain ischemia; OGD; NF-κB/RelA; HATs; HDACs; polyphenols; green tea; resveratrol

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Faggi, L.; Porrini, V.; Lanzillotta, A.; Benarese, M.; Mota, M.; Tsoukalas, D.; Parrella, E.; Pizzi, M. A Polyphenol-Enriched Supplement Exerts Potent Epigenetic-Protective Activity in a Cell-Based Model of Brain Ischemia. Nutrients 2019, 11, 345.

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