Department of Pharmacology, Faculty of Pharmacy, University of Seville, Profesor García González Street 2, 41012 Seville, Spain.
Biochem Pharmacol. 2011 Oct 1;82(7):737-45. doi: 10.1016/j.bcp.2011.06.043. Epub 2011 Jul 7.
Current epidemiological and experimental studies support a beneficial role of dietary polyphenols in several gastrointestinal diseases, including inflammatory bowel disease. The aim of this study was to gain a better understanding of the effects of a naturally occurring polyphenol, ellagic acid, present in some fruits such as pomegranate, raspberries and nuts among others, in an experimental murine model of Crohn's disease by intra-colonic administration of TNBS in rats. Analysis of the lesions were carried out by macroscopic and histological technics. Inflammation response was assessed by histology and myeloperoxidase activity. iNOS and COX-2 are upregulated by MAPKs and NF-κB nuclear transcription factor in intestinal epithelial cells thus, we determined the expression of iNOS, COX-2 and the involvement of the p38, JNK, ERK1/2 MAPKs and NF-κB signalling in the protective effect of EA by western blotting. Oral administration of EA (10-20 mg/kg) diminished the severity and extension of the intestinal injuries induced by TNBS although there was no observed a significant dose-response. In addition, EA increased mucus production in goblet cells in colon mucosa, decreased neutrophil infiltration and pro-inflammatory proteins COX-2 and iNOS overexpression. Also EA was capable of reducing the activation of p38, JNK and ERK1/2 MAPKs, preventing the inhibitory protein IκB-degradation and inducing an inhibition of the nuclear translocation level of p65 in colonic mucosa. In conclusion, EA reduces the damage in a rat model of Crohn's disease, alleviates the oxidative events and returns pro-inflammatory proteins expression to basal levels probably through MAPKs and NF-κB signalling pathways.
目前的流行病学和实验研究支持膳食多酚在几种胃肠道疾病中的有益作用，包括炎症性肠病。本研究旨在通过在大鼠中结肠内给予 TNBS，更好地了解天然存在的多酚——存在于某些水果（如石榴、覆盆子和坚果等）中的鞣花酸——在克罗恩病实验模型中的作用。通过宏观和组织学技术分析病变。通过组织学和髓过氧化物酶活性评估炎症反应。iNOS 和 COX-2 被 MAPKs 和 NF-κB 核转录因子在上皮细胞中上调，因此，我们通过 Western blot 确定了 iNOS、COX-2 的表达以及 p38、JNK、ERK1/2 MAPKs 和 NF-κB 信号通路在 EA 保护作用中的参与。口服 EA（10-20mg/kg）可减轻 TNBS 诱导的肠道损伤的严重程度和范围，尽管未观察到明显的剂量反应。此外，EA 增加了结肠黏膜中杯状细胞的粘蛋白产生，减少了中性粒细胞浸润和促炎蛋白 COX-2 和 iNOS 的过度表达。此外，EA 能够减少 p38、JNK 和 ERK1/2 MAPKs 的激活，防止抑制蛋白 IκB 的降解，并诱导核易位水平的 p65 在结肠黏膜中的抑制。总之，EA 可减轻大鼠克罗恩病模型中的损伤，减轻氧化应激事件，并使促炎蛋白的表达恢复到基础水平，可能通过 MAPKs 和 NF-κB 信号通路。
