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- Title
Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.
- Authors
Koh, Seong-Joon; Choi, Youn-I; Kim, Yuri; Kim, Yoo-Sun; Choi, Sang Woon; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae
- Abstract
Purpose: Walnuts (Juglans regia) are known to have anti-cancer and immunomodulatory effects. However, little information is available on the effects of walnut phenolic extract (WPE) on intestinal inflammation and colitis-associated colon cancer. Methods: COLO205 cells were pretreated with WPE and then stimulated with tumor necrosis factor (TNF)-α. In the acute colitis model, wild type mice (C57BL/6) were administered 4% dextran sulfate sodium (DSS) for 5 days. In the chronic colitis model, interleukin (IL)-10−/− mice were administered with either the vehicle or WPE (20 mg/kg) by oral gavage daily for 2 weeks. In an inflammation-associated tumor model, wild type mice were administered a single intraperitoneal injection of azoxymethane followed by three cycles of 2% DSS for 5 days and 2 weeks of free water consumption. Results: WPE significantly inhibited IL-8 and IL-1α expression in COLO205 cells. WPE attenuated both the TNF-α-induced IκB phosphorylation/degradation and NF-κB DNA binding activity. The administration of oral WPE significantly reduced the severity of colitis in both acute and chronic colitis models, including the IL-10−/− mice. In immunohistochemical staining, WPE attenuated NF-κB signaling in the colons of both colitis models. Finally, WPE also significantly reduced tumor development in a murine model of colitis-associated colon cancer (CAC). Conclusions: WPE ameliorates acute and chronic colitis and CAC in mice, suggesting that WPE may have potentials for the treatment of inflammatory bowel disease.
- Subjects
ANIMAL experimentation; CARCINOGENS; CELL lines; CELLULAR signal transduction; COLITIS; COLON (Anatomy); COLON tumors; DEXTRAN; EPITHELIAL cells; GENE expression; IMMUNOHISTOCHEMISTRY; INFLAMMATORY mediators; INTRAPERITONEAL injections; INTERLEUKINS; INTESTINAL mucosa; MICE; ORAL drug administration; PHENOLS; PHOSPHORYLATION; STAINS &; staining (Microscopy); TUMOR necrosis factors; WALNUT; DNA-binding proteins; PLANT extracts; SEVERITY of illness index; DISEASE complications; PHARMACODYNAMICS
- Publication
European Journal of Nutrition, 2019, Vol 58, Issue 4, p1603
- ISSN
1436-6207
- Publication type
Article
- DOI
10.1007/s00394-018-1704-3