Immunomodulatory Effect of Ginsenoside Rb2 Against Cyclophosphamide-Induced Immunosuppression in Mice

Abstract

Ginsenoside Rb2 (Rb2), a fundamental saponin produced and isolated from ginseng (Panax ginseng C.A. Meyer), has a wide range of biological actions. The objective of this investigation was to see if ginsenoside Rb2 has any immunomodulatory properties against cyclophosphamide (CTX)-induced immunosuppression. For the positive control group, levamisole hydrochloride (LD) was used. We discovered that intraperitoneal injection of Rb2 (5, 10, 20 mg/kg) could relieve CTX-induced immunosuppression by enhanced immune organ index, reduced the pathological characteristics of immunosuppression, promoted natural killer (NK) cells viability, improved cell-mediated immune response, boosted the IFN-γ (Interferon-gamma), TNF-α (Tumor necrosis factor-alpha), IL-2 (Interleukin-2), and IgG (Immunoglobulin G), as well as macrophage activity like carbon clearance and phagocytic index. Rb2 significantly elevated the mRNA expression of IL-4 (Interleukin-4), SYK (Tyrosine-protein kinase-SYK), IL-2, TNF-α, and IL-6 (Interleukin-6) in the spleen of CTX-injected animals. Molecular docking results showed that Rb2 had excellent binding properties with IL-4, SYK, IL-2, TNF, and IL-6, indicating the target protein might be strongly correlated with the immunomodulatory effect of Rb2. Taken together, ginsenoside Rb2 can improve the immune function that is declined in CTX-induced immunosuppressed mice, the efficacy maybe due to the regulation of related cytokine and mRNA expression.

Keywords: cyclophosphamide; ginsenoside Rb2; immune regulation; immunosuppression; side effect.

FIGURE 1

Histopathology observation of spleen. (A) ×100, (B) ×100, (C) ×400.

FIGURE 2

Effect of ginsenoside Rb2 on ConA- and LPS- induced splenocyte proliferation, on NK cells activity, carbon clearance capacityin and the cytokines in CTX induced immunosuppressive mice. (A), ConA-induced splenocyte proliferation; (B), LPS-induced splenocyte proliferation; (C), NK cells activity; (D,E), carbon clearance capacityin; (F), IFN-γ; (G), TNF-α; (H), IgG; (I), IL-2. The data was expressed as mean ± S. D (n = 20). ##p < 0.01, compared to Normal. *p < 0.05; **p < 0.01, compared to Model.

FIGURE 3

The relative gene expression of cytokines in spleen. (A), IL-2; (B), IL-4; (C), IL-6; (D), SYK; (E), TNF-α. ##p < 0.01, compared to Normal. **p < 0.01, compared to Model. (F) Docking of Rb2 (yellow) into the binding site of mouse IL-2 (PDB code: 4yue, green); (G) Docking of Rb2 (yellow) into the binding site of mouse IL-4 (PDB code: 2b8u, green); (H) Docking of Rb2 (yellow) into the binding site of mouse IL-6 (PDB code: 2l3y, green); (I) Docking of Rb2 (yellow) into the binding site of mouse SYK (PDB code: 2mc1, green); (J) Docking of Rb2 (yellow) into the binding site of mouse TNF (PDB code: 2tnf, green).