Anti-inflammatory Effects of Proanthocyanidin-rich Cranberry Extract through the Suppression of NF-kB Pathway and Histone Acetylase in RAW 264.7 and Mouse Bone Marrow-derived Macrophages

Seok-Yeong Yu¹, Jungbae Oh¹, Justin S. Kim^{1, 2}, Young-In Kwon³, Emmanouil Apostolidis⁴ and Young-Cheul Kim^1,

¹Department of Nutrition, University of Massachusetts, Amherst, MA 01003

²Division of Nutrition of Nutritional Sciences, University of Illinois, Urbana-Champaign, IL 61802

³Department of Food and Nutrition, Hannam University, Daejeon, 34054 Korea

⁴Department of Chemistry and Food Science, Framingham State University, Framingham, MA 01701

Cite this paper:
Seok-Yeong Yu, Jungbae Oh, Justin S. Kim, Young-In Kwon, Emmanouil Apostolidis and Young-Cheul Kim. Anti-inflammatory Effects of Proanthocyanidin-rich Cranberry Extract through the Suppression of NF-kB Pathway and Histone Acetylase in RAW 264.7 and Mouse Bone Marrow-derived Macrophages. Journal of Food and Nutrition Research. 2021; 9(2):79-86. doi: 10.12691/jfnr-9-2-4

Abstract

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-κB (NF-κB) 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-κB p65-mediated inflammatory responses. The objective of the study was to investigate if proanthocyanidin (PAC)-rich cranberry extract (CBE) suppresses histone acetylation and NF-κB 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, Tnfα, 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.

Keywords:
cranberry extract histone deacetylation NF- κB activation inflammation RAW264.7 macrophage mouse bone marrow-derived macrophage

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