Abstract

FCP alleviates CTX-induced immunosuppression in mice. • FCP enhances APC-related activation marker expression in BMDCs and macrophages. • FCP promotes immune recovery in bone marrow, spleen, and intestine. • FCP modulates gut microbiota composition during immune recovery. Wine-processed Fructus Corni, prepared from the dried mature fruits of Cornus officinalis , is a traditional Chinese processed food containing biologically active polysaccharides with multiple pharmacological effects, including antihyperglycemic and immunomodulatory activities. However, the restorative mechanisms of wine-processed Fructus Corni polysaccharides (FCP) under immunosuppression have not yet been reported. This study investigated the effects of FCP on the activation of antigen-presenting cells (APCs) in vitro and assessed their impact on immune function and gut microbiota in cyclophosphamide (CTX)-induced immunosuppressed mice. The results demonstrated that FCP significantly enhanced the expression of CD80, CD86 and CD40 on bone marrow-derived dendritic cells (BMDCs) and RAW 264.7 macrophages. In CTX-treated mice, oral administration of FCP at doses of 100, 300, and 500 mg/kg mitigated weight loss, immune organ damage, and hematological abnormalities in CTX-treated mice. It restored lymphocyte subset balance in bone marrow, spleen, and intestinal lymph nodes, and promoted the recovery of immunoglobulins (IgM, IgA, IgG, sIgA) and cytokines (IL-4, IL-6, IFN-γ), and corrected gut microbiota dysbiosis by enriching beneficial bacteria. In summary, FCP showed systemic immunomodulatory effects in CTX-treated mice. This effect may be associated with improved APC-related activation marker expression, recovery of lymphocyte subset distribution, and gut microbiota remodeling, highlighting the potential of FCP as a functional immunoregulatory food ingredient.