Superiority of ultrasound-extracted Flammulina velutipes polysaccharides over hot water-extracted ones in mitigating colonic cell pyroptosis: Discoveries into modulation of NLRP3 pathway.

Flammulina velutipes is a major edible fungus with abundant yield and mature industrial production technology. Its main functional component, Flammulina velutipes polysaccharide, has huge development and utilization value. In light of the current uncertainty regarding the mechanisms by which Flammulina velutipes polysaccharides prevent colonic cell pyroptosis, the mechanisms of ultrasound-extracted Flammulina velutipes polysaccharide (FVPU2) in inhibiting colonic cell pyroptosis in mice were investigated, and compared with Flammulina velutipes polysaccharide extracted via hot water extraction (FVPH2). The findings showed that FVPU2 more potently inhibited inflammation-induced impairment of Caco-2 monolayer barrier integrity than FVPH2 (p < 0.05). Additionally, FVPU2 effectively downregulated pro-inflammatory cytokine production while enhancing tight junction protein and growth factor expression (p < 0.05). FVPU2 can inhibit the expression of TLR4, MyD88, and ASC proteins more effectively than FVPH2 (p < 0.05). In animal models, FVPU2 reduced the disease activity index and spleen index, decreased pro-inflammatory cytokine concentrations, extended colon length, enhanced tight junction protein and intestinal acid mucus expression, and improved the gut microbiota's capacity to produce short-chain fatty acids. Notably, FVPU2 significantly inhibited excessive NLRP3 signaling pathway-related protein expression during intestinal epithelial cell pyroptosis, demonstrating its remarkable activity and potential for preventing colitis. The findings could facilitate the development of intestinal health foods derived from FVPU2.