Auricularia auricula Polysaccharide Extracted Under Ultrahigh Pressure: Structural Characterization and Immunomodulatory Mechanism

Ultrahigh‐pressure (UHP) treatment can reconfigure polysaccharide structures to enhance their immunomodulatory activity. This study compared the structural and immunomodulatory properties of Auricularia auricula polysaccharides extracted by hot water (AAP) and ultrahigh‐pressure‐assisted (UAAP) methods. Structural analysis revealed that UAAP exhibited a lower molecular weight (Mw (15,333 Da), Mn (11,167 Da)) with a narrower polydispersity index, indicating superior homogeneity. Although both shared similar monosaccharide compositions and thermal stability below 200°C, UAAP displayed a more porous and irregular morphology. In a cyclophosphamide‐induced immunosuppressed mouse model, both polysaccharides promoted recovery of immune organ indices and phagocytic function. They also upregulated key serum cytokines (TNF‐α, IFN‐γ, IL‐1β, IL‐2, IL‐4) and immunoglobulins (IgA, IgG, IgM) in a concentration‐dependent manner. Mechanistically, UAAP/AAP activated the MAPK/NF‐κB pathway by enhancing the phosphorylation of p38, JNK, and NF‐κB p65, and promoting nuclear translocation of NF‐κB p65. Overall, UAAP demonstrated superior immunomodulatory activity. Correlation analysis further revealed distinct association patterns between individual monosaccharides and MAPK/NF‐κB signaling indicators, with weighted prediction suggesting stronger pathway activation potential for UAAP than AAP. This study provides an experimental basis for the efficient extraction and immunomodulatory application of Auricularia auricula polysaccharides.