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

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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.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education [Grant Number. NRF-2014R1A1A2057695(S-JK)], [2016-R1D1A1B03931961(S-JK)], by a multidisciplinary research grant-in-aid from the Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center (02-2015-01) and by a Grant from California Walnut Commission.

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Authors and Affiliations

  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

    Seong-Joon Koh, Youn-I Choi, Ji Won Kim, Byeong Gwan Kim & Kook Lae Lee

  2. Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, South Korea

    Yuri Kim & Yoo-Sun Kim

  3. Chaum Life Center, CHA University School of Medicine, Seoul, South Korea

    Sang Woon Choi

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  1. Seong-Joon Koh
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Correspondence to Kook Lae Lee.

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Koh, SJ., Choi, YI., Kim, Y. et al. Walnut phenolic extract inhibits nuclear factor kappaB signaling in intestinal epithelial cells, and ameliorates experimental colitis and colitis-associated colon cancer in mice. Eur J Nutr 58, 1603–1613 (2019). https://doi.org/10.1007/s00394-018-1704-3

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