title: Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism.
abstract: The objectives of this study were to compare the anti-inflammatory effects of anthocyanins from blueberry (BBA), blackberry (BKA), and blackcurrant (BCA) and to determine the relationship between their antioxidant capacity and anti-inflammatory effect in macrophages. Major anthocyanins in BBA, BKA and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BKA showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 μg/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1β (IL-1β) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 μg/ml or higher. Tumor necrosis factor α (TNFα) mRNA levels and secretion were also significantly decreased in LPS-treated macrophages. The levels of the repression were comparable for all berry anthocyanins. LPS-induced nuclear factor κB (NF-κB) p65 translocation to the nucleus was markedly attenuated by all of the berry anthocyanins. In bone marrow-derived macrophages (BMMs) from nuclear factor E2-related factor 2 wild-type (Nrf2(+/+)) mice, BBA, BKA and BCA significantly decreased cellular reactive oxygen species (ROS) levels with a concomitant decrease in IL-1β mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1β mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BKA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-κB independent of the NRF2-mediated pathways.
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Sang Gil
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Bohkyung
authors.initials: B
authors.lastname: Kim
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Tho X
authors.initials: TX
authors.lastname: Pham
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Manatou
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Sung I
authors.initials: SI
authors.lastname: Koo
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Ock K
authors.initials: OK
authors.lastname: Chun
authors.affiliation: Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06269, USA. Electronic address: ji-young.lee@uconn.edu.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology*; D029798:Blueberry Plants / Q000737:chemistry; D005960:Glucosides / Q000032:analysis; D007249:Inflammation / Q000178:diet therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D031965:Ribes / Q000737:chemistry; D065856:Rubus / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000872:Anthocyanins; D005960:Glucosides; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C462279:cyanidin-3-O-beta-glucopyranoside; C010705:delphinidin-3-rutinoside; C458419:malvidin-3-glucoside
keywords: Anthocyanins; Antioxidant capacity; Berries; Inflammation; NF-κB; NRF2