A mixed levan fructan from Rohdea japonica mitigates ulcerative colitis induced by dextran sulfate sodium via regulating intestinal microbiota mediated pyroptosis.

Ulcerative colitis (UC) is a global health challenge, prompting the development of novel treatments. Polysaccharides have shown promise in UC therapy. In this study, in vivo experiments with Drosophila demonstrated that the crude polysaccharide (RJ60) from Rohdea japonica (Thunb.) Roth exhibits significant anti-UC activity. Further purification identified a homogeneous polysaccharide, RJP60-1, with a degree of polymerization of 20, was a mixed levan fructan. Structural analysis revealed that RJP60-1 is predominantly linked by →2)-β-D-Fruf-(1→, →2)-β-D-Fruf-(6→, and →2,6)-β-D-Fruf-(1→ glycosidic bonds. Biological activity results demonstrated that RJP60-1 exhibited significant anti-UC therapeutic effects, including alleviation of weight loss, improved disease activity index scores, reduced colon shortening, and restoration of intestinal tissue integrity. RJP60-1 modulated the expression of inflammatory markers (TNF-α, IL-1β, and IL-10), oxidative stress indicators (MDA, SOD, and GSH), and tight junction proteins (ZO-1, Occludin), thereby enhancing intestinal barrier function. Additionally, RJP60-1 modulated the gut microbiota by increasing beneficial bacteria such as Bacteroidetes and suppressing pathogenic bacterial flora including Firmicutes. This modulation led to an increased content of short-chain fatty acids (SCFAs), which helped alleviate inflammation in UC by inhibiting the pyroptosis pathway. These findings suggested that RJP60-1 could serve as a promising therapeutic agent for treating UC.