Investigation of the immunoregulatory mechanisms of total saponins from black ginseng

Objective: This study aimed to elucidate the immune-regulating effects and underlying mechanisms of action of total saponins extracted from black ginseng in an immunosuppressed murine model. Methods: The chemical composition of black ginseng total saponins (BGTS) was analyzed using high-performance liquid chromatography, which revealed a high content of rare ginsenosides, such as Rk1, Rg5, and Rg3. Immunosuppressed mice were administered BGTS, and key immunological parameters were assessed, including body weight, spleen and thymus indices, cytokine and immunoglobulin levels, and the expression of immune-related genes and proteins. Results: BGTS treatment significantly improved body weight and immune organ indices and promoted the secretion of cytokines, including interleukin (IL) 2, IL-1β, tumor necrosis factor-alpha, immunoglobulin (Ig) A, IgG, and IgM. Mechanistically, BGTS significantly activated the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88/nuclear factor-κB signaling pathway at the protein level and upregulated gene expression of TLR-4, TNF-α, IL-6, and IL-1β. Conclusion: These findings suggest that BGTS exerts notable immunomodulatory effects by enhancing innate immune responses, primarily by activating the TLR4-mediated signaling pathway. Further studies are necessary to isolate the contribution of individual ginsenosides and evaluate the long-term safety and clinical potential of BGTS.