Dietary phenolic acids attenuate multiple stages of protein glycation and high-glucose-stimulated proinflammatory IL-1β activation by interfering with chromatin remodeling and transcription in monocytes

This study examined the effects of dietary phenolic acids on individual stages of protein glycation and utilized monocyte cultures to assess whether these phytochemicals modulate the activation of proinflammatory cytokine under high glucose (HG, 15 mmol/L) conditions mimicking diabetes. In vitro glycation assays showed that a number of phenolic acids exerted inhibitory effects on the glycation reaction and its subsequent crosslinking. Phenolic acids, especially methoxyphenolic acids, prevented increase in both levels of the interleukin-1 beta (IL-1 beta) and oxidative stress caused by HG. The effect appeared to be mediated by modulation of the protein kinase C/nuclear factor-kappa B axis. Chromatin immunoprecipitation demonstrated for the first time that HG increased the recruitment of nuclear factor-kappa B p65 and CREB-binding protein to the IL-1 beta promoter. Interestingly, HG also increased histone acetylation and methylation within the IL-1 beta promoter and decreased histone deacetylase activities in monocytes, thus facilitating chromatin remodeling and transcription. Such inappropriate inflammatory responses were found to be controlled effectively by treatment with methoxyphenolic compounds. In conclusion, this study suggests that phenolic acids could exert their anti-inflammatory activities as antiglycation agents and as modifiers of signaling pathways. It provides evidence for a novel mechanism by which phenolics supplementation might have additional protective effects against diabetic complications.