Abstract: Objective: To assess the mitigative effects of plant-derived organic selenium on ulcerative colitis (UC). Methods: Selenium-containing proteins (SePro) and peptides (SePP) were prepared from natural selenium-enriched Cardamine L. in Ankang, Shaanxi province by alkali dissolution followed by acid precipitation and enzymatic hydrolysis, respectively. A mouse model of UC was induced by 3 g/100 mL dextran sulphate sodium (DSS) solution. Commercial selenium-enriched yeast tablets and mesalazine enteric-coated tablets were used as positive controls, and a control group, a DSS group, a DSS + mesalazine enteric-coated tablet group, a DSS + selenium-enriched yeast tablet group, a DSS + SePro group, and a DSS + SePP group were set up. The control group drank water freely, while all other groups drank 3 g/100 mL DSS solution intermittently. The disease activity index (DAI) score, spleen index, and colon length of the mice were recorded, histopathological changes of the colon were analyzed by hematoxylin and eosin staining, the expression of colonic barrier proteins was detected by immunohistochemistry, the levels of inflammatory cytokines in colonic tissues were detected by real-time quantitative polymerase chain reaction, short chain fatty acids (SCFAs) in the feces were quantified by gas chromatography-mass spectrometry, and the gut microbiota was analyzed by 16S rRNA gene sequencing to reveal the ameliorative effects of SePro and SePP on DSS-induced UC mice. Results: Both SePro and SePP alleviated the symptoms of UC in mice (body mass loss, increased DAI score and spleen index), repaired the damage of colonic tissues, up-regulated the expression of the colonic barrier protein mucin 2 (MUC2), down-regulated the mRNA expression levels of inflammatory cytokines: Caspase-1, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), interleukin 1β (IL-1β), interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), and cyclooxygenase 2 (COX-2) in colonic tissues, promoted the growth of intestinal beneficial bacteria, inhibited the proliferation of harmful bacteria, and increased the fecal content of SCFAs. Further comparison showed that SePro was superior to SePP in maintaining and increasing the expression of MUC2 and inhibiting the mRNA expression of Caspase-1, TNF-α, and COX-2, while SePP was superior to SePro in inhibiting body mass loss, decreasing DAI score and spleen index, down-regulating the mRNA expression of NLRP3, IL-1β, and IFN-γ and increasing the fecal content of SCFAs. In addition, although selenium-enriched yeast tablets had the best effect in inhibiting body mass loss in mice, and mesalazine enteric-coated tablets had the best effect in reducing DAI score, the effects of SePro and SePP were generally better than those of commercial mesalazine enteric-coated tablets and selenium yeast tablets in reducing spleen index, alleviating colonic histopathological injury, up-regulating the expression of MUC2, down-regulating the mRNA expression of inflammatory cytokines and increasing the fecal content of SCFAs. Conclusion: SePro and SePP have preventive and ameliorative effects against DSS-induced ulcerative colitis in mice by repairing colonic mucosal injury, inhibiting inflammatory response, enhancing colonic barrier function, and regulating the balance of gut microbiota. Therefore, SePro and SePP have the potential to be developed as dietary supplements for intestinal health.

Key words: selenium-enriched Cardamine L.; ulcerative colitis; selenium-containing proteins; selenium-containing peptides; gut microbiota; inflammatory response