School of Food Science.
Department of Animal Science, Washington State University, Pullman, WA.
J Nutr. 2018 May 1;148(5):667-674. doi: 10.1093/jn/nxy007.
Ulcerative colitis causes recurring intestinal mucosal injury and sustained inflammation, increasing the likelihood of colorectal cancer (CRC) development. Dietary red raspberry (RB) is a rich source of phytonutrients known to have anti-inflammatory activity; however, the role of RB on CRC prevention in chronic colitis has not been examined.
This study examined the effects of dietary RB supplementation on inflammation, epithelium repair, and oncogenic signaling in dextran sulfate sodium (DSS)-induced chronic colitis in mice.
Six-week-old male C57BL/6J mice were fed a control or RB (5% of dry feed weight; n = 12/group) diet for 10 wk. Starting from the fourth week, mice were administered 2 repeated cycles of 1% DSS (7-d DSS treatment plus 14-d recovery) and were monitored daily for disease activity index (DAI) score. Colonic tissues were collected at the end of the study for histochemical, immunohistochemical, and biochemical analysis of inflammation, differentiation and proliferation markers.
RB supplementation reduced the DAI score and histologic damage (by 38.9%; P ≤ 0.01), expression of inflammatory mediators (by 20-70%; P ≤ 0.01), infiltration of CD4 T cells (by 50%; P ≤ 0.05), and α4β7 integrin and related adhesion molecules (by 33.3%; P ≤ 0.01). Furthermore, RB supplementation facilitated epithelium repair, as evidenced by enhanced goblet cell density, expression of transcription factors including Kruppel-like factor 4 (Klf4) and Hairy and enhancer of split 1 (Hes1), terminal differentiation markers, mucin 2 (Muc2), and intestinal alkaline phosphatase (by 20-200%; P ≤ 0.01). Conversely, proliferating cell nuclear antigen (by 70%; P ≤ 0.01), β-catenin, and signal transducer and activator of transcription 3 (STAT3) signaling (by 19-33%; P ≤ 0.05) were reduced by RB supplementation. In addition, RB supplementation enhanced p53 stability (by 53%) and reduced oncogenic gene expression (by 50-60%).
RB supplementation reduced DAI score and the risk of CRC development during recurring colitis in mice, suggesting that RB is a possible dietary supplement for patients with ulcerative colitis and related gut inflammatory diseases.
溃疡性结肠炎导致反复发作的肠道黏膜损伤和持续炎症，增加了结直肠癌（CRC）发展的可能性。树莓是一种富含植物营养素的食物，具有抗炎活性；然而，树莓对慢性结肠炎 CRC 的预防作用尚未被研究。
本研究旨在探讨饮食中添加树莓对葡聚糖硫酸钠（DSS）诱导的慢性结肠炎小鼠炎症、上皮修复和致癌信号的影响。
6 周龄雄性 C57BL/6J 小鼠喂食对照或树莓（占干饲料重量的 5%；n=12/组）饮食 10 周。从第四周开始，小鼠接受 2 次 1% DSS（7 天 DSS 处理加 14 天恢复）重复周期，并每天监测疾病活动指数（DAI）评分。研究结束时收集结肠组织，进行组织化学、免疫组织化学和生化分析，以评估炎症、分化和增殖标志物。
树莓补充剂可降低 DAI 评分和组织学损伤（降低 38.9%；P≤0.01）、炎症介质表达（降低 20-70%；P≤0.01）、CD4 T 细胞浸润（降低 50%；P≤0.05）和 α4β7 整合素和相关粘附分子（降低 33.3%；P≤0.01）。此外，树莓补充剂促进了上皮修复，表现为杯状细胞密度增加、转录因子包括 Kruppel 样因子 4（Klf4）和 Hairy 和增强子分裂 1（Hes1）、终末分化标志物、黏蛋白 2（Muc2）和肠道碱性磷酸酶（增加 20-200%；P≤0.01）的表达增加。相反，增殖细胞核抗原（增加 70%；P≤0.01）、β-连环蛋白和信号转导和转录激活因子 3（STAT3）信号（降低 19-33%；P≤0.05）被树莓补充剂降低。此外，树莓补充剂增强了 p53 稳定性（增加 53%）并降低了致癌基因表达（降低 50-60%）。
树莓补充剂可降低反复发作结肠炎小鼠的 DAI 评分和 CRC 发展风险，表明树莓可能是溃疡性结肠炎和相关肠道炎症性疾病患者的一种饮食补充剂。
