Department of Pharmacology, School of Pharmacy, University of Seville, 41012 Seville, Spain.
J Nutr Biochem. 2013 Jul;24(7):1401-13. doi: 10.1016/j.jnutbio.2012.11.008. Epub 2013 Jan 18.
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.
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。