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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

  • Seong-Joon Koh
  • Youn-I Choi
  • Yuri Kim
  • Yoo-Sun Kim
  • Sang Woon Choi
  • Ji Won Kim
  • Byeong Gwan Kim
  • Kook Lae Lee
Original Contribution

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

Walnut Inflammatory bowel disease Nuclear factor kappaB Colon cancer 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Seong-Joon Koh
    • 1
  • Youn-I Choi
    • 1
  • Yuri Kim
    • 2
  • Yoo-Sun Kim
    • 2
  • Sang Woon Choi
    • 3
  • Ji Won Kim
    • 1
  • Byeong Gwan Kim
    • 1
  • Kook Lae Lee
    • 1
  1. 1.Department of Internal Medicine, Seoul National University Boramae HospitalSeoul National University College of MedicineSeoulSouth Korea
  2. 2.Department of Nutritional Science and Food ManagementEwha Womans UniversitySeoulSouth Korea
  3. 3.Chaum Life CenterCHA University School of MedicineSeoulSouth Korea

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