Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray–Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.

Highlights

  • Inflammatory bowel disease (IBD) is a chronic relapsing immune-inflammatory condition of the gastrointestinal (GI) tract with increasing prevalence worldwide [1]

  • The severity of the dextran sulfate sodium (DSS)-induced colitis, disease activity index (DAI), colon length, macroscopic score, and histological score was significantly improved by saffron at a 20 mg/Kg dose while saffron at the dose of 10 mg/Kg showed improvement in the DAI, macroscopic score, and histological score (Figure 1B–F)

  • The results indicate that saffron reduces the severity of DSS-induced colitis in mice by improving the gross and histopathological characteristics of the colonic mucosa

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Summary

Introduction

Inflammatory bowel disease (IBD) is a chronic relapsing immune-inflammatory condition of the gastrointestinal (GI) tract with increasing prevalence worldwide [1]. IBD is broadly classified into Crohn’s disease (CD) and ulcerative colitis (UC) on the basis of their clinical presentation, but the risk factors implicated on the pathogenesis of both CD and UC are similar [2]. The etiology of IBD is complex and various studies suggest that its pathogenesis is associated with a dysregulated immune response, genetic factors, gut microbiota, and environmental factors [2]. Failure in managing IBD over the long run deteriorates the inflammatory conditions and increases the risk of developing colon cancer [6,7,8,9,10].

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