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This study investigated the potential immunomodulatory effects of fermented soybean extract (FSE) in RAW264.7 cells and BALB/c mice. The expression of proinflammatory cytokines in RAW264.7 cells was measured after LPS stimulation in the presence or absence of FSE. Mice were orally administered 125, 250, and 500 mg/kg FSE for 21 days, and their immune response was analyzed. In RAW264.7 cells, FSE significantly reduced the expression of proinflammatory cytokines.  In vivo  experiments revealed significantly elevated splenocyte proliferation; neutrophil migration; phagocytic activities; expression of CD18 + , CD4 + , and CD8 +  T cells; and expression of IL-2, IL-4, and IFN-γ. The major compounds in FSE were identified by GC–MS and by LC–MS/MS. Molecular docking analysis showed that daidzin, genistin and daidzein could potentially bind to the human high-affinity FcγRI–IgG complex to be involved in immunological responses. Taken together, FSE can be a candidate ingredient for health functional food with enhanced immunomodulating ability.

Immunomodulatory effects of Bacillus subtilis -fermented soybean extract in mice