Sanghuangporus vaninii Polysaccharide Hydrogel Attenuates DNFB ‐Induced Atopic Dermatitis in Mice via Immunomodulation

ABSTRACT Atopic dermatitis (AD), a prevalent chronic inflammatory skin disorder, highlights the need for advanced immunomodulatory therapies. We isolated three novel polysaccharides (SVP1–SVP3) from Sanghuangporus vaninii , characterized their physicochemical properties, and formulated them into hydrogels. These were applied to 2,4‐dinitrofluorobenzene (DNFB)‐induced AD mouse models to investigate their therapeutic effects and underlying mechanisms. SVP hydrogels, notably SVP3, significantly attenuated AD pathology including scratching frequency, dermatitis severity, epidermal hyperplasia, and mast cell infiltration compared to the blank hydrogel control. Crucially, SVP3 alleviated immune dysregulation by lowering CD4 + T cells and increasing CD8 + T cells, suppressing the secretion of both Th1 and Th2 signature cytokines, and remodeling the disordered inflammatory cytokine network. Mechanistic analysis indicated suppressed activation of the TLR4/MyD88/NF‐κB pathway accompanied by decreased protein expression, alongside inhibited nuclear translocation of p‐NF‐κB p65 and p‐STAT3. Our findings suggest that SVP3 alleviates AD symptoms partly through modulation of TLR4/MyD88/NF‐κB signaling, supporting its value as a promising therapeutic strategy for immunomodulation in inflammatory skin disorders.