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膳食特级初榨橄榄油多酚补充剂可调节 DSS 诱导的小鼠慢性结肠炎。

Dietary extra virgin olive oil polyphenols supplementation modulates DSS-induced chronic colitis in mice.

机构信息

Department of Pharmacology, School of Pharmacy, University of Seville, 41012 Seville, Spain.

出版信息

J Nutr Biochem. 2013 Jul;24(7):1401-13. doi: 10.1016/j.jnutbio.2012.11.008. Epub 2013 Jan 18.

Abstract

We evaluated the protective effect of dietary extra virgin olive oil (EVOO) polyphenol extract (PE) supplementation in the inflammatory response associated to chronic colitis model. Six-week-old mice were randomized in four dietary groups: standard diet (SD), EVOO diet and both enriched with PE (850 ppm) (SD+PE and EVOO+PE). After 30 days, animals that were exposed to dextran sodium sulfate (DSS) (3%) followed by 3 weeks of drinking water developed chronic colitis, which was evaluated by disease activity index (DAI) and histology. Cell proliferation was analyzed by immunohistochemical and changes in monocyte chemotactic protein (MCP)-1 and tumor necrosis factor (TNF)-α mRNA expression by quantitative real-time polymerase chain reaction. Colonic expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein kinases (MAPKs), IκBα inhibitory and peroxisome proliferator-activated receptor gamma (PPARγ) were determined by western blotting. SD-DSS group showed a significant increase of DAI, histological damage and cell proliferation, as well as an up-regulation of TNF-α, MCP-1, COX-2 and iNOS proteins. p38 and JNK MAPKs phosphorylation, IκBα degradation and PPARγ deactivation were also observed. However, in DSS-treated and EVOO+PE-fed mice, DAI and cell proliferation were significantly reduced, as well as MCP-1, TNF-α, COX-2 and iNOS expression levels. In addition, this dietary group, notably down-regulated JNK phosphorylation, prevented IκBα degradation and PPARγ deactivation. These results demonstrated, for the first time, that EVOO-PE supplementation possessed marked protective effects on experimental colitis through PPARγ up-regulation and nuclear transcription factor-kappa B and MAPK signaling pathway inhibition, decreasing the inflammatory cascade. We concluded that PE-enriched EVOO diet could be a beneficial functional food on ulcerative colitis.

摘要

我们评估了膳食特级初榨橄榄油(EVOO)多酚提取物(PE)补充剂对慢性结肠炎模型相关炎症反应的保护作用。6 周龄的小鼠被随机分为四组饮食:标准饮食(SD)、EVOO 饮食以及同时富含 PE(850ppm)的饮食(SD+PE 和 EVOO+PE)。30 天后,暴露于葡聚糖硫酸钠(DSS)(3%)的动物随后饮用 3 周水,发展为慢性结肠炎,通过疾病活动指数(DAI)和组织学进行评估。通过免疫组织化学分析细胞增殖,通过定量实时聚合酶链反应分析单核细胞趋化蛋白(MCP)-1 和肿瘤坏死因子(TNF)-α mRNA 表达的变化。通过 Western 印迹测定结肠诱导型一氧化氮合酶(iNOS)、环氧化酶(COX)-2、丝裂原活化蛋白激酶(MAPKs)、IκBα 抑制和过氧化物酶体增殖物激活受体γ(PPARγ)的表达。SD-DSS 组显示 DAI、组织损伤和细胞增殖显著增加,以及 TNF-α、MCP-1、COX-2 和 iNOS 蛋白的上调。还观察到 p38 和 JNK MAPKs 磷酸化、IκBα 降解和 PPARγ 失活。然而,在 DSS 处理和 EVOO+PE 喂养的小鼠中,DAI 和细胞增殖显著减少,以及 MCP-1、TNF-α、COX-2 和 iNOS 表达水平降低。此外,该饮食组显著下调 JNK 磷酸化,防止 IκBα 降解和 PPARγ 失活。这些结果首次表明,EVOO-PE 补充剂通过上调 PPARγ 和核转录因子-κB 和 MAPK 信号通路抑制,减少炎症级联反应,对实验性结肠炎具有显著的保护作用。我们得出结论,富含 PE 的 EVOO 饮食可能是溃疡性结肠炎的有益功能性食品。

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