Inhibition of the pro-inflammatory NF-κB pathway by a grape seed and grape marc meal extract in intestinal epithelial cells
Inhibition of the pro-inflammatory NF-κB pathway by a grape seed and grape marc meal extract in intestinal epithelial cells
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DOI：
10.1111/j.1439-0396.2011.01222.x
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发表时间：
2012-12-01
影响因子：
2.7
通讯作者：
Eder, K.
中科院分区：
文献类型：
--
作者：
Gessner, D. K.;Ringseis, R.;Eder, K.
在猪和其他单胃动物中，断奶阶段通常伴随着对肠道疾病(如腹泻)的易感性增加，这是因为在断奶期间在肠道中诱导了炎症过程。鉴于肠道炎症对动物的饲料消耗、肠道消化能力和生长发育的不利影响，控制肠道炎症是保持家畜生产性能的合理途径。因此，本研究旨在研究一种商品化的富含多酚葡萄籽(GS)和葡萄马克粉(GM)的饲料添加剂在一个成熟的体外肠上皮模型(极化的Caco-2细胞)中的抗炎作用。通过研究从GS和GM粉基饲料添加剂中获得的乙醇提取物(GSGME)对促炎转录因子NF-kappa B的影响来评价其抗炎作用，该转录因子被认为在诱导断奶相关肠炎中起关键作用。最高非细胞毒性浓度的乙醇GSGME可剂量依赖性地降低肿瘤坏死因子α诱导的Caco-2肠道细胞核因子-kappa B反式激活，并降低肿瘤坏死因子α诱导的靶基因IL-1β、IL-8、MCP-1和CXCL1的mRNA水平(p<；0.05)。乙醇GSGME对Caco-2细胞中的Nrf2途径没有影响，表现为Nrf2的反式激活和Nrf2靶基因如GPX-2、NQO1、CYP1A1和UGT1A1的mRNA水平没有变化。综上所述，本研究表明乙醇GSGME在体外条件下对肠道细胞具有抗炎作用。因此，富含多酚的GSGM粉基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存在不适当的核因子-kappa B激活状态时，如断奶阶段。未来的研究将证明以GSGM为基础的饲料添加剂的体内抗炎潜力。
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-kappa B, 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 TNF alpha-induced NF-kappa B transactivation and decreased TNF alpha-induced mRNA levels of the NF-kappa B target genes IL-1 beta, 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-kappa B 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.