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Eur J Nutr. 2019 Jun;58(4):1603-1613. doi: 10.1007/s00394-018-1704-3. Epub 2018 May 9.

Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice.

Author information

1
Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 5 Gil 20, Boramae-Road, Dongjak-Gu, Seoul, 156-707, South Korea.
2
Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, South Korea.
3
Chaum Life Center, CHA University School of Medicine, Seoul, South Korea.
4
Department of Internal Medicine, Seoul National University Boramae Hospital, Seoul National University College of Medicine, 5 Gil 20, Boramae-Road, Dongjak-Gu, Seoul, 156-707, South Korea. kllee@brmh.org.

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.

KEYWORDS:

Colon cancer; Inflammatory bowel disease; Nuclear factor kappaB; Walnut

PMID:
29744610
DOI:
10.1007/s00394-018-1704-3

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