Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice

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.

Egg white peptides administration in enhancing pathological immune response and regulating intestinal bacteria abundance: A new strategy for relieving young mice colitis

“…For example, changes in intestinal flora can lead to a decrease in SCFAs, which indirectly reduces Treg cells and further aggravates colitis (Shen et al, 2019). By lowering proinflammatory cytokine levels and regenerating intestinal epithelial cells, SCFAs have ameliorated colitis (Banskota et al, 2021;Parada Venegas et al, 2019).…”

“…For example, changes in intestinal flora can lead to a decrease in SCFAs, which indirectly reduces Treg cells and further aggravates colitis (Shen et al., 2019). By lowering proinflammatory cytokine levels and regenerating intestinal epithelial cells, SCFAs have ameliorated colitis (Banskota et al., 2021; Parada Venegas et al., 2019). Although Lactobacillus cannot directly produce SCFAs, its metabolite lactic acid can be utilized by bacteria of all kinds, such as Clostridium propionicum, Propionibacterium , and many other bacteria to ferment acetic acid and propanoic acids (Li, Chen, et al., 2022; Sato et al., 2021).…”

An examination into the mental and physical effects of a saffron extract (affron®) in recreationally-active adults: A randomized, double-blind, placebo-controlled study

“…It has also been demonstrated in several studies that saffron and its constituents can have a relaxant effect on blood vessels and other smooth muscles, possibly by activating ß2-adrenoceptors, inhibiting histamine H1 and muscarinic receptors and calcium channels, and modulating concentrations of nitric oxide [ 60 ]. Moreover, because the gut microbiome can affect vagus nerve activity [ 61 ], and saffron can alter gut microbiota [ 62 , 63 ], this presents as another potential mechanism of action associated with saffron intake. Finally, the anti-inflammatory and antioxidant effects of saffron may account for its positive effects on mood and HRV in males [ 64 ].…”

Saffron extract (Safr'Inside™) improves anxiety related behaviour in a mouse model of low-grade inflammation through the modulation of the microbiota and gut derived metabolites

“…Of the limited evidence available, saffron's anti-inflammatory properties are most frequently cited, 28 along with modulation of the monoaminergic neurotransmission 22,23 and oxidative stress, 27 indicating that these mechanisms may be an integral part of the process. Despite evidence of saffron-mediated gut microbial shift, 29,30 this has not been explored in the context of mental health/anxiety.…”