Epigenetic modulation of mechanisms involved in inflammation: Influence of selected polyphenolic substances on histone acetylation state

In the present study, we have investigated the influence of low concentrations of polyphenols (5 μM) on histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity, a monocyte cell system related to the inflammatory process. We selected gallic acid, ellagic acid, oenothein B, valoneic acid dilactone and penta- O -galloyl-β- d -glucose, which are known to affect inflammatory responses, such as IL-6 secretion and/or NF-κB down-regulation and polyphenol metabolites (urolithins A, B and C). TNF-α stimulation resulted in a reduction of THP-1 cell viability by 28.9%, reduced HDAC activity from 25.2 to 13.5 pmol/μg protein and increased HAT activity from 24.0 to 45.5 pmol/μg protein. The coincubation with ellagic acid and oenothein B restored the viability and reversed the effect of TNF-α on HAT and HDAC activities. Urolithins B and C, gallic acid and penta- O -galloyl-β- d -glucose only showed significant reductions of HAT activity, by 40–50%. Our results prove that polyphenols act as epigenetic modulators.