Bevifimod

Different extraction solvents significantly influence the properties and bioactivity of polysaccharides. In this study, water- and alkaline-extracted polysaccharides from Schizophyllum commune (SPW and SPA) were prepared using an ultrasonic-assisted method, and their physicochemical properties and anti-obesity activities were compared. SPA had a significantly higher extraction yield (15.86 %), Mw (220.86 kDa) and glucose/mannose molar ratio (26.54:1) than SPW (with values of 8.95 %, 23.86 kDa and 4.49:1, respectively), whereas SPW showed better thermal stability and in vitro antioxidant activity than SPA. Both SPW and SPA supplementation effectively mitigated weight gain, reduced hepatic damage, improved lipid metabolism and intestinal barrier function, and reversed gut dysbiosis in mice. However, SPW showed better anti-obesity effects than SPA, which may stem from its lower Mw and ability to promote the proliferation of Ligilactobacillus murinus and Romboutsia ileals. These results showed that SPW has the potential to be a functional food additive for obesity management.

The progression of ulcerative colitis (UC) involves immune dysregulation, intestinal barrier dysfunction, and microbial dysbiosis while existing targeted therapies present challenges, including adverse effects and economic burdens. UC is characterized by persistent intestinal inflammation, manifesting as abdominal pain, hematochezia, and malnutrition. Prolonged uncontrolled inflammation may lead to colorectal cancer or severe complications, significantly impairing quality of life. Recent studies have revealed a significant correlation between pathological accumulation of senescent cells and UC pathogenesis, suggesting anti-senescence therapeutics as potential interventions. In this study, we identified sparfloxacin (SPA), a fluoroquinolone antibiotic, through high-throughput screening as an effective senolytic agent that markedly alleviates DSS-induced murine colitis. Mechanistically, combining cellular and animal experiments with transcriptomic, untargeted metabolomic, and metagenomic analyses, we demonstrated sparfloxacin's tripartite therapeutic effects: ① Senescence inhibition via downregulation of p16/p21 expression; ② Effective suppression of aberrant JAK/NF-κB signaling activation with a concomitant reduction in pro-inflammatory cytokines (TNF-α, IL-6); ③ Gut microbiota remodeling characterized by increased probiotic abundance and elevated levels of beneficial metabolites. This study for the first time elucidates the molecular mechanism whereby SPA ameliorates UC through coordinated multi-target actions involving senescence inhibition, anti-inflammatory effects, and microbiome restoration. Our findings not only expand the clinical applications of fluoroquinolones but also provide a theoretical foundation for developing integrated UC treatment strategies targeting cellular senescence.