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

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• 作者：Sang Gil Lee^a ; Bohkyung Kim^a ; Yue Yang^a ; Tho X. Pham^a ; Young-Ki Park^a ; Jose Manatou^b ; Sung I. Koo^a ; Ock K. Chun^a ; Ji-Young Lee^a ; ^{ji-young.lee@uconn.edu" class="auth_mail}
• 关键词：BBA ; blueberry anthocyanin fraction ; BCA ; blackcurrant anthocyanin fraction ; BKA ; blackberry anthocyanin fraction ; LPS ; lipopolysaccharide ; NRF2 ; nuclear factor E2-related factor 2 ; IL-1尾 ; interleukin-1尾 ; TNF伪 ; tumor necrosis factor 伪 ; ROS ; reactive oxygen species ; NF-魏B ; nuclear factor 魏B ; GAPDH ; glyceraldehyde 3-phosphate dehydrogenase ; TBP ; TATA-binding protein ; AAPH ; 2 ; 2&prime ; -Azobis(2-methylpropionamidine) dihydrochloride ; ABTS ; 2 ; 2&prime ; -azino-bis(3-ethylbenzothiazoline-6-sulphonic
• 刊名：Journal of Nutritional Biochemistry
• 出版年：April, 2014
• 年：2014
• 卷：25
• 期：4
• 页码：404-411
• 全文大小：950 K

文摘

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 渭g/ml of BBA, BKA and BCA, and subsequently activated by lipopolysaccharide (LPS) to measure proinflammatory cytokine production. Interleukin 1尾 (IL-1尾) messenger RNA (mRNA) levels were significantly decreased by all berry anthocyanins at 10 渭g/ml or higher. Tumor necrosis factor 伪 (TNF伪) 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 魏B (NF-魏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尾 mRNA levels upon LPS stimulation. However, in the BMM from Nrf2^{鈭?鈭?/sup>} mice, the anthocyanin fractions were able to significantly decrease IL-1尾 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-魏B independent of the NRF2-mediated pathways.