Investigation of the Immunoregulatory Mechanisms of Fermented Ginseng Freeze–Dried Powder Enriched in Rare Ginsenosides

Background Immunosuppression can impair immune homeostasis and increase susceptibility to various diseases, highlighting the need for effective and safe immunomodulatory agents. Fermentation can enhance the bioavailability and transformation of ginsenosides into rare ginsenosides, which may contribute to the immunomodulatory potential of ginseng. Purpose To investigate the immunoregulatory mechanisms of fermented ginseng freeze–dried powder enriched in rare ginsenosides in cyclophosphamide-induced immunodeficient mice. Materials and Methods Immunodeficiency was induced by cyclophosphamide, followed by oral administration of fermented ginseng powder at different doses. Body weight was recorded. Serum immunoglobulins were measured by enzyme-linked immunosorbent assay (ELISA), immune-related proteins by Western blot, and immune gene expression by real-time quantitative polymerase chain reaction (RT-qPCR). Results Fermented ginseng significantly attenuated immunosuppression-induced weight loss, with the strongest effect at the high dose. ELISA showed increased serum immunoglobulin G (IgG), immunoglobulin M (IgM), and cytotoxic T lymphocyte (CD8+) levels in treated groups. Western blot revealed upregulation of Bcl-2-associated X protein (Bax) and Caspase-3 and downregulation of B-cell lymphoma 2 (Bcl-2). Expression levels of myeloid differentiation primary response 88 (MyD88), toll-like receptor (TLR)-4, and nuclear factor kappa B (NF-κB) were dose-dependently restored. RT-qPCR confirmed increased TLR-2, TLR-4, interleukin (IL)-2, and IL-3 transcription and reduced IL-6 expression. Conclusion Fermented ginseng enriched in rare ginsenosides enhances immune function in immunodeficient mice by modulating immune cells, promoting apoptosis-related pathways, and regulating innate immune signaling, with the high dose showing the greatest effect.