eng Science and Education Publishing Journal of Food and Nutrition Research 2333-1240 2021-02-26 9 2 79 86 10.12691/jfnr-9-2-4 JFNR2021924 article Seok-Yeong Yu 1 Jungbae Oh 1 Justin S. Kim 1 2 Young-In Kwon 3 Emmanouil Apostolidis 4 Young-Cheul Kim yckim@nutrition.umass.edu 4 Department of Nutrition, University of Massachusetts, Amherst, MA 01003 Department of Food and Nutrition, Hannam University, Daejeon, 34054 Korea Department of Chemistry and Food Science, Framingham State University, Framingham, MA 01701 Obesity-mediated chronic inflammation promotes the progression of obesity to metabolic anti-inflammatory effect of cranberries by decreasing plasma inflammatory cytokines. However, its specific mechanisms of action remain unclear. The nuclear factor-百B (NF-百B) pathway in macrophages plays a critical role in regulating the expression of many inflammatory genes, and histone acetylation has been identified as a key epigenetic modification for the NF-百B p65-mediated inflammatory responses. The objective of the study was to investigate if proanthocyanidin (PAC)-rich cranberry extract (CBE) suppresses histone acetylation and NF-百B p65 activation in RAW 264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs). Treatment with 5% and 15% PAC-containing CBEs markedly suppressed the expression of pro-inflammatory mediators (iNos, Cox-2, Tnf汐, Mcp-1 and Il-6) in both RAW 264.7 macrophages and BMDMs stimulated with lipopolysaccharides (LPS). CBE significantly reduced LPS-induced phosphorylation of p65 in both cell types without changing total p65 expression levels. Moreover, 15% PAC-CBE increased the expression levels of histone deacetylase 3 (HDAC3) with a concomitant decrease in histone H4 acetylation levels. These results suggest that CBE increases HDAC3 protein expression with the subsequent inhibition of p65 phosphorylation to mediate anti-inflammatory effects in macrophages. Cranberries may serve as a dietary agent to attenuate chronic inflammation in patients with obesity and related complications. http://pubs.sciepub.com/jfnr/9/2/4/jfnr-9-2-4.pdf cranberry extract histone deacetylation NF- 百B activation inflammation RAW2647 macrophage mouse bone marrow-derived macrophage