Ginsenoside Rg3 (Rg3), which comprises Panax ginseng, is commonly used to improve the immunocompetence of cancer patients undergoing chemotherapy. This study was designed to elucidate the immunoenhancement effects of Rg3 in immunosuppressed mice induced by cyclophosphamide (CTX) treatment. Balb/c mice were administered Rg3 intragastrically once daily for 19 consecutive days and were intraperitoneally administered CTX (80 mg/kg) on days 15-19. Weight and immune organ indices were recorded. Hematological tests and cytokines were assessed using ELISA. We measured the activity of LDH and ACP, performed pathological and immunohistochemical staining of immune organs, and evaluated cytokines and transcription factors using RT-PCR. Immunosuppressed mice showed weight loss, decreased thymus and spleen indices and severe pathological damage. CTX attenuated macrophage phagocytosis by decreasing activity of LDH and ACP and decreased the release of related immune factors, IgG, IL-2 and G-CSF. Subsequently, we observed T lymphocyte expression on the surface of the thymus and spleen, which inhibited T cell activity. Further mechanistic analysis showed that CTX decreased the expression of T-bet and IFN-γ and increased the expression of GATA-3 and IL-4 in the thymus and spleen, which affected the Th1/Th2 balance. However, Rg3 treatment reversed CTX-induced immunosuppression. In summary, all the results suggest that Rg3 has protective effects on CTX-induced immunosuppression, which could be partially related to macrophages, T cells and Th1/Th2 balance. Although deeper studies of its mechanism are needed, these findings support the hypothesis that Rg3 can improve the reduced immunocompetence after CTX injury.
Keywords: Cyclophosphamide; Ginsenoside Rg3; Immunosuppressive; T lymphocyte; Th1/Th2.
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