Structural characterization of Taiwanofungus camphoratus polysaccharide and its ameliorative effects on myelosuppression and immunosuppression by regulating macrophage activation.

Chemotherapy-induced myelosuppression and immunosuppression impair anticancer efficacy, while macrophages maintain hematopoietic and immune homeostasis. The potential of Taiwanofungus camphoratus polysaccharides to alleviate these two conditions through macrophage modulation remains unexplored. This study focuses on a bioactive polysaccharide from Taiwanofungus camphoratus mycelium, aiming to characterize it and explore its molecular mechanism in alleviating myelosuppression and immunosuppression. Using advanced purification and analytical techniques, we identified a Taiwanofungus camphoratus polysaccharide (ACPSA) which has two structural domains: a heteroglucan constructed with →4) -α-D-Glcp -(1→ and →6)-α-D-Galp-(1→ backbone linkages; and, β-glucan constituents featuring linear →6)-β-D-Glcp-(1→ and →3)-β-D-Glcp-(1→ polymeric frameworks. Using mouse models of myelosuppression and immunosuppression, along with macrophage models, we found that ACPSA alleviates damage to the bone marrow and immune organs, restores hematopoietic stem/progenitor cell differentiation, normalizes leukocyte depletion, and corrects macrophage abnormalities by upregulating classical activation markers. Morphometric and immunoblot analyses demonstrated that ACPSA enhances classical macrophage activation and phagocytic capacity in vitro. ACPSA promoted macrophage reconstitution and activation in vivo. This study employs proteomics to explore the molecular mechanisms of ACPSA's biological functions. It has been verified that ACPSA enhances classical macrophage activation and phagocytic function by suppressing macrophage autophagy. This mechanism highlights its therapeutic potential in addressing chemotherapy-induced complications.