Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism

Berry anthocyanins suppress the expression and secretion of proinflammatory mediators in macrophages by inhibiting nuclear translocation of NF-κB independent of NRF2-mediated mechanism
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DOI:
10.1016/j.jnutbio.2013.12.001
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发表时间:
2014-04-01
影响因子:
5.6
通讯作者:
Lee, Ji-Young
Lee, Ji-Young
中科院分区:
医学2区
文献类型:
--
作者:
Lee, Sang Gil;Kim, Bohkyung;Lee, Ji-Young

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本研究的目的是比较蓝莓(BBA),黑莓(BKA),黑加仑(BCA)的花青素的抗炎作用,并确定它们的抗氧化能力和抗炎作用之间的关系在巨噬细胞。BBA、BM和BCA中主要花色苷为锦葵色素-3-葡萄糖苷(16%)、矢车菊色素-3-葡萄糖苷(98%)和飞燕草色素-3-芸香糖苷(44%)。BM的总抗氧化能力高于BBA和BCA。将RAW 264.7巨噬细胞与0-20 μ g/ml的BBA、BM和BCA孵育,随后通过脂多糖(LPS)活化以测量促炎细胞因子的产生。白细胞介素1 β(IL-1 β)信使RNA(mRNA)水平被10 μ g/ml或更高浓度的所有浆果花青素显著降低。在LPS处理的巨噬细胞中,肿瘤坏死因子α(TNF α)mRNA水平和分泌也显著降低。所有浆果花青素苷的阻遏水平是可比的。LPS诱导的核因子-κ B(NF-κ B)p65易位到细胞核显着减弱所有的浆果花青素。在来自核因子E2相关因子2野生型(Nrf 2(+/+))小鼠的骨髓源性巨噬细胞(BCG)中,BBA、BKA和BCA显著降低了LPS刺激后细胞活性氧(ROS)水平,同时降低了IL-1 β mRNA水平。然而,在来自Nrf 2(-/-)小鼠的BMM中,花青素组分能够显著降低IL-1 β mRNA,尽管ROS水平没有受到显著影响。总之,BBA、BRA和BCA在巨噬细胞中发挥其抗炎作用,至少部分是通过抑制NF-κ B的核转位,而不依赖于NRF 2介导的途径。(C)2014爱思唯尔公司All rights reserved.
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, BM and BCA were malvidin-3-glucoside (16%), cyanidin-3-glucoside (98%) and delphinidin-3-rutinoside (44%), respectively. BM showed higher total antioxidant capacity than BBA and BCA. RAW 264.7 macrophages were incubated with 0-20 mu g/ml of BBA, BM and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1 beta (IL-1 beta) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 mu g/ml or higher. Tumor necrosis factor alpha (TNF alpha) 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 kappa B (NF-kappa B) 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-1 beta mRNA levels upon LPS stimulation. However, in the BMM from Nrf2(-/-) mice, the anthocyanin fractions were able to significantly decrease IL-1 beta mRNA despite the fact that ROS levels were not significantly affected. In conclusion, BBA, BRA and BCA exert their anti-inflammatory effects in macrophages, at least in part, by inhibiting nuclear translocation of NF-kappa B independent of the NRF2-mediated pathways. (C) 2014 Elsevier Inc. All rights reserved.