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葡萄籽油和葡萄渣提取物对肠道上皮细胞中促炎 NF-κB 通路的抑制作用。

Inhibition of the pro-inflammatory NF-κB pathway by a grape seed and grape marc meal extract in intestinal epithelial cells.

机构信息

Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Gießen, Heinrich-Buff-Ring 26-32, Gießen, Germany.

出版信息

J Anim Physiol Anim Nutr (Berl). 2012 Dec;96(6):1074-83. doi: 10.1111/j.1439-0396.2011.01222.x. Epub 2011 Sep 7.

DOI:10.1111/j.1439-0396.2011.01222.x
PMID:21895782
Abstract

In pigs and other monogastric animal, the weaning phase is commonly accompanied by an increased susceptibility to gut disorders such as diarrhoea owing to the induction of an inflammatory process in the intestine during weaning. Given the unfavourable effects of intestinal inflammation on feed consumption, digestive capacity of the intestine and growth of animals, controlling intestinal inflammation is a reasonable approach for the maintenance of performance characteristics of livestock animals. Therefore, this study aimed to study the anti-inflammatory potential of a commercial polyphenol-rich grape seed (GS) and grape marc (GM) meal-based feed additive in a well-established in vitro intestinal epithelium model (polarized Caco-2 cells). The anti-inflammatory potential was evaluated by studying the effect of an ethanolic extract obtained from the GS and GM meal-based feed additive (GSGME) on the pro-inflammatory transcription factor NF-κB, which is considered to play a key role in the induction of weaning-associated intestinal inflammation. The highest non-cytotoxic concentrations of the ethanolic GSGME dose dependently reduced TNFα-induced NF-κB transactivation and decreased TNFα-induced mRNA levels of the NF-κB target genes IL-1β, IL-8, MCP-1 and CXCL1 in Caco-2 intestinal cells (p < 0.05). No effect of the ethanolic GSGME was observed on the cytoprotective Nrf2 pathway in Caco-2 cells as evidenced by an unaltered Nrf2 transactivation and unchanged mRNA levels of Nrf2 target genes, such as GPX-2, NQO1, CYP1A1 and UGT1A1. In conclusion, this study shows that an ethanolic GSGME exerts anti-inflammatory effects in intestinal cells under in vitro conditions. Thus, polyphenol-rich GSGM meal-based feed additives may be useful for the inhibition or prevention of inflammatory processes in the intestine of livestock animals, in particular during states with inappropriate NF-κB activation in the intestinal tissue, such as the weaning phase. Future studies are warranted to prove the in vivo anti-inflammatory potential of GSGM meal-based feed additives.

摘要

在猪和其他单胃动物中,断奶期通常伴随着肠道疾病易感性增加,如腹泻,这是由于断奶期间肠道内发生炎症过程。鉴于肠道炎症对饲料采食量、肠道消化能力和动物生长的不利影响,控制肠道炎症是维持家畜生产性能的合理方法。因此,本研究旨在研究一种基于商业多酚丰富的葡萄籽(GS)和葡萄渣(GM)的饲料添加剂的抗炎潜力,该添加剂在成熟的体外肠上皮模型(极化 Caco-2 细胞)中进行研究。通过研究来自 GS 和 GM 饲料添加剂(GSGME)的乙醇提取物对促炎转录因子 NF-κB 的影响来评估抗炎潜力,NF-κB 被认为在诱导与断奶相关的肠道炎症中发挥关键作用。乙醇 GSGME 的最高非细胞毒性浓度依赖地减少了 TNFα 诱导的 NF-κB 转录激活,并降低了 Caco-2 肠道细胞中 TNFα 诱导的 NF-κB 靶基因 IL-1β、IL-8、MCP-1 和 CXCL1 的 mRNA 水平(p<0.05)。在 Caco-2 细胞中,乙醇 GSGME 对细胞保护 Nrf2 途径没有影响,这表现为 Nrf2 转录激活没有改变,Nrf2 靶基因如 GPX-2、NQO1、CYP1A1 和 UGT1A1 的 mRNA 水平也没有改变。总之,本研究表明,在体外条件下,乙醇 GSGME 对肠道细胞具有抗炎作用。因此,富含多酚的 GSGM 基于饲料添加剂可能有助于抑制或预防家畜肠道中的炎症过程,特别是在肠道组织中 NF-κB 激活不当的情况下,如断奶期。需要进一步的研究来证明 GSGM 基于饲料添加剂的体内抗炎潜力。

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