Food, Nutrition, and Health, Faculty of Land and Food Systems, University of British Columbia, 2205 East Mall, Vancouver, BC V6T 1Z4, Canada.
Mol Cell Biochem. 2012 May;364(1-2):147-57. doi: 10.1007/s11010-011-1213-7. Epub 2012 Jan 11.
A glucose-lysine (Glu-Lys) Maillard reaction mixture heated at 121°C for 60 min was processed by ultrafiltration, ethyl acetate extraction, and semi-preparative HPLC to recover a bioactive fraction, termed F3. F3, characterized by spectral analysis to contain three distinct components, inhibited NO and IL-8 by 70 and 61%, respectively, at a concentration of 50 μg/ml in inflamed Caco-2 cells induced by IFN-γ and phorbol 12-myristate 13-acetate (PMA). F3 significantly (P < 0.05) down-regulated several genes involved in nuclear factor kappa B (NF-κB) signaling pathway. These genes included the cytokine receptors, TNFRSF10A and TNFRSF10B; receptor-associated proteins, IRAK2 and TICAM1; the inhibitor κB kinase, IKBKE; the NF-κB inhibitor, NFKBIA; and the NF-κB subunits, REL, RELA, and RELB. F3 also down-regulated the NF-κB responsive genes IL-8, NOS2, and ICAM1, attenuated the gene expression of peroxidases such as DUOX1 and DUOX2, and relieved the down-regulated GCFHR that are involved in the biosynthesis of NO and TROAP, a gene suppressed by NO. The anti-inflammatory activity of F3 was mediated through multiple processes that included regulation of gene expressions involved in NF-κB signaling, the inhibition of IL-8 and iNOS translation, a decrease in NO synthesis and attenuating oxidative stress in inflamed Caco-2 cells. Our results show that MRP components have the potential to suppress inflammation in IFN-γ and PMA-induced Caco-2 cells.
葡萄糖-赖氨酸(Glu-Lys)美拉德反应混合物在 121°C 下加热 60 分钟,通过超滤、乙酸乙酯萃取和半制备 HPLC 进行处理,以回收具有生物活性的部分,称为 F3。F3 通过光谱分析鉴定为含有三个不同的成分,在浓度为 50μg/ml 时,分别抑制了由 IFN-γ和佛波醇 12-肉豆蔻酸 13-乙酸酯(PMA)诱导的炎症 Caco-2 细胞中的 NO 和 IL-8,抑制率分别为 70%和 61%。F3 显著(P<0.05)下调了几个参与核因子 kappa B(NF-κB)信号通路的基因。这些基因包括细胞因子受体 TNFRSF10A 和 TNFRSF10B;受体相关蛋白 IRAK2 和 TICAM1;NF-κB 抑制剂激酶 IKBKE;NF-κB 抑制剂 NFKBIA;以及 NF-κB 亚基 REL、RELA 和 RELB。F3 还下调了 NF-κB 反应基因 IL-8、NOS2 和 ICAM1,减弱了过氧化物酶如 DUOX1 和 DUOX2 的基因表达,并缓解了参与 NO 和 TROAP 生物合成的 GCFHR 的下调,NO 抑制了 TROAP 的表达。F3 的抗炎活性是通过多种途径介导的,包括调节 NF-κB 信号通路相关基因的表达,抑制 IL-8 和 iNOS 的翻译,减少 NO 的合成,减轻炎症 Caco-2 细胞中的氧化应激。我们的结果表明,MRP 成分具有抑制 IFN-γ和 PMA 诱导的 Caco-2 细胞炎症的潜力。