Structural characterization of a novel polysaccharide fraction from Hericium erinaceus and its signaling pathways involved in macrophage immunomodulatory activity

Hericium erinaceus polysaccharide (HEP-W) can significantly stimulate the immunomodulatory activity on murine macrophages. [Display omitted] •Immunostimulating polysaccharide (HEP-W) was purified from Hericium erinaceus.•Structure of HEP-W was characterized by HPGPC, GC, FT-IR and NMR.•HEP-W promoted macrophage phagocytosis and increased the secretion of NO and cytokines.•The pattern recognition receptors of HEP-W were elucidated for the first time.•HEP-W exhibited potent immunomodulating activity through MyD88/IRAK-1/TRAF-6/PI3K/AKT/MAPKs signaling pathways. A novel heteropolysaccharide fraction (HEP-W) with great immunomodulatory activity was isolated from the fruiting bodies of Hericium erinaceus. Structural characterization revealed that HEP-W had an average molecular weight of 1.59×104 Da and was composed of rhamnose, fucose, mannose, glucose and galactose at a molar ratio of 0.98:1.59:0.89:5.60:7.06. The main glycosidic linkage types of HEP-W consisted of (1→)-α-D-Glc, (1→3,6)-α-D-Glc, (1→2,6)-α-D-Gal, T-β-Gal, (1→3,4)-β-D-Man, (1→3)-α-Rha, and (1→2)-β-L-Fuc by periodate oxidation-Smith degradation and NMR analysis. The bioactivity tests showed that HEP-W could significantly promote the pinocytic and phagocytic capacity and increase the NO, IL-6 and TNF-α secretion by activating corresponding mRNA expression in macrophages through MyD88/IRAK-1/TRAF-6/PI3K/AKT/MAPKs signaling pathways. Meanwhile, toll-like receptor 2 and mannose receptor were found to act as synergistic PRRs to co-regulate the immunomodulatory response to HEP-W in macrophages. These findings provide a molecular basis for the application of HEP-Was a natural immunoregulatory agent in functional foods.