Ameliorative effect of an acidic polysaccharide from Phellinus linteus on ulcerative colitis in a DSS-induced mouse model

Abstract

Phellinus linteus, a rare medicinal fungus, displays strong antitumor and anti-inflammatory activities because of its active metabolites, particularly polysaccharides. We investigated effects of P. linteus acidic polysaccharide (PLAP) on amelioration of dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in a mouse model, and associated mechanisms. PLAP treatment alleviated major UC symptoms (weight loss, reduced food intake, increased disease activity index), and ameliorated histopathological colon tissue damage, reduced levels of pro-inflammatory factors (TNF-α, IL-6, IL-1β), enhanced anti-inflammatory factor IL-10 level, reduced levels of oxidative stress-related enzymes iNOS and MPO, and enhanced expression of tight junction proteins (ZO-1, occludin, claudin-1). qPCR analysis revealed that PLAP downregulated phosphorylation levels of p65 and p38 and transcriptional level of TLR-4. High-throughput sequencing showed that PLAP restored gut microbiota diversity and species abundances in the UC model, and gas chromatographic analysis showed that it increased levels of beneficial short-chain fatty acids. Our findings indicate that PLAP has strong potential for development as an anti-UC agent based on its reduction of inflammation and oxidative stress levels, modulation of gut microbiota composition, and promotion of normal intestinal barrier function.