Abstract

This study aimed to investigate the protective potential of genistein in dextran sulfate sodium (DSS)-induced colonic injury in vitro and in vivo models. The results showed that DSS exposure caused growth suppression, colonic injury, inflammation, and barrier dysfunction in mice. Dietary genistein alleviated DSS-caused colonic injury via reducing colonic weight, rectal bleeding, and diarrhea ratio. Meanwhile, genistein reduced colonic inflammatory response via downregulating cytokines expression and improved colonic permeability and barrier in DSS-challenged mice. In Caco-2 cells, genistein improved cell viability and cellular permeability and inhibited DSS-induced activation of TLR4/NF-κB signal. In conclusion, genistein alleviated DSS-caused colonic injury, inflammation, and gut dysfunction, which might be associated with the TLR4/NF-κB signal.

Highlights

  • Various dietary nutrients have been identified as potential adjuvants to prevent different chronic diseases and ameliorate pharmacological therapies, such as inflammatory bowel disease (IBD)

  • The present data showed that dietary genistein attenuated colonic injury via improving colonic weight, rectal bleeding, and www.impactjournals.com/oncotarget diarrhea ratio, suggesting a protective role of genistein in dextran sulfate sodium (DSS)-induced colonic injury in mice

  • Dietary supplementation with genistein inhibited the overexpression of IL-1β and IFN-γ, suggesting an anti-inflammatory functions in DSS-induced colonic inflammation

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Summary

Introduction

Various dietary nutrients have been identified as potential adjuvants to prevent different chronic diseases and ameliorate pharmacological therapies, such as inflammatory bowel disease (IBD). A soy derived isoflavanoid compound serves as a potent agent in both prophylaxis and treatment of cancer and various other chronic diseases [1]. Studies about genistein mainly focuses on its preventative and therapeutic effects for cancers [2, 3]. Genistein acts as an anti-cancer agent mainly by mediating apoptosis process, cell cycle, and angiogenesis and inhibiting metastasis. Genistein has been showed anti-inflammatory effect in various models [4]. Genistein at physiological concentrations (0.1 μM-5 μM) inhibits tumor necrosis factor α (TNF-α)induced endothelial inflammatory response and vascular inflammation in C57BL/6 mice via mediating the protein kinase pathway A [5]. Various reports have shown that genistein inactivates nuclear factor-kappa B (NF-κB) signal [6, 7], which is widely associated with the development and pathological mechanism of inflammatory diseases [8, 9]

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