Polysaccharide from Pyrus pashia Buch ameliorates DSS-induced colitis in mice via MAPKP38/NF-κB P65 and SCFAs/ERK/MSK signaling pathways

Abstract

Purpose

In this experiment, we investigated the effect of Pyrus pashia Buch on the relevant inflammatory disease indexes, intestinal microbiota, and short-chain fatty acids in mice with dextran sodium sulfate (DSS)-induced ulcerative colitis.

Methods

The anti-inflammatory effect of PPBP was assessed by measuring inflammatory markers (ELISA), colonic pathological changes (H&E), qPCR of relevant gene expression, 16S rRNA sequencing of intestinal contents, and short-chain fatty acids (SCFAs).

Results

Pyrus pashia Buch polysaccharide (PPBP) alleviated the main symptoms of UC (Weight down, reduced diet, increased disease activity index) and ameliorated pathological damage to colonic tissues by reducing the release of cytokines TNF-α, IL-6, IL-1β, and iNOS. Furthermore, PPBP enhanced the expression of tight junction proteins (ZO-1, Occludin, and Claudin-1) and elevated intestinal mucin MUC2 and MUC3 levels. qPCR analysis showed that PPBP activated MAPK/NF-κB and verified that it regulated the MAPK signaling pathway through the SCFA-ERK-MSK pathway and downregulated the phosphorylation levels of p38 and p65. Using the 16S rRNA method to analyze the level of microbial changes in the mouse gut, it was shown that Pyrus pashia Buch polysaccharide (PPBP) restored the intestinal microbial diversity and species richness in the UC model, and gas chromatography-mass spectrometry analysis demonstrated that Pyrus pashia Buch polysaccharide (PPBP) was able to increase beneficial short chain fatty acids.

Conclusion

PPBP is a resourceful edible herb. By studying the mechanism of action of P38/IκBα/P65 in MAPK/NF-κB and SCFA with ERK/MSK in MAPK, we have demonstrated that PPBP can attenuate inflammatory responses to repair intestinal mucosal damage, balance abnormalities in the intestinal microbiota, and improve the function of the damaged intestinal barrier. It provides preliminary experiments for developing PPBP as an IκBα stabilizer and P65 inhibitor.