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Background   Cordyceps militaris (C. militaris)  is reported to exert various immune-activities. To enhance its activity, we fermented  C.militaris  with  Pediococcus pentosaceus  ON89A (GRC-ON89A). In this study, we investigated the immune-enhancing activity GRC-ON89A, using immunosuppressed model.    Methods  Immunosuppression was induced by intraperitoneal injection of cyclophosphamide (CY). Each group was orally administered distilled water, GRC-ON89A or GRC, respectively. The phagocytic activities against IgG -opsonized FITC particles were measured using phagocytosis assay kit. The contents β-glucan, cordycepin and SCFA were measured using β-glucan kit, liquid chromatography-mass spectrometry analysis and Gas chromatography-mass spectrometry analysis, respectively.    Results  Among GRC fermented with different probiotic strains ( Pediococcus pentossaceus  ON89A,  Lactobacillus pentosus  SC64,  Weissella cibaria  Sal.Cla22), GRC-ON89A induced the highest elevation of nitric oxide production and enhanced phagocytic activity of RAW 264.7 cells. In primary cultured murine macrophages from normal and CY-treated mice, GRC-ON89A increased phagocytic activity, compared to that in control cells. GRC-ON89A also significantly induced the mRNA expression of TNF-α and IL-10 and the levels of phosphorylated Lyn, Syk and MAPK. The contents of β-glucan, cordycepin and SCFA in GRC significantly increased after ON89A fermentation, compared to those in unfermented GRC.    Conclusion  These results indicate that GRC-ON89A exerted the enhanced immunostimulatory activity and contained more nutritional components, compared to unfermented GRC. Our results suggested that GRC-ON89A may be applied as an agent for immune boosting therapy in immune suppressed patients.

Immune-enhancing activity of C. militaris fermented with Pediococcus pentosaceus (GRC-ON89A) in CY-induced immunosuppressed model