Synergistic Immunostimulating Effects Of Red Ginseng Acidic Polysaccharide And Pidotimod And The Underlying Mechanisms

We investigated the synergistic effect of combined treatment with red ginseng acidic polysaccharide(RGAP) from Panax ginseng C.A.Meyer and pidotimod in immunosuppressed mice,which provides a reference for the combinational application of western and oriental medicines.First,the combination of pidotimod and RGAP restored concanavalin A-induced splenic T cell proliferation and LPS-stimulated B cell proliferation significantly.The production of nitric oxide(NO) from peritoneal macrophages was increased by the combinations.NK cell activity was increased by RGAP alone or in combination with pidotimod.A synergistic increase in the level of serum IL-12 and interferon-gamma was observed when the combination of the two was used.RGAP alone or in combination with pidotimod modulated the level of serum C-reactive protein to a near-normal level.These results indicate that combinations of pidotimod and RGAP are synergistic and suggest that combination therapy using pidotimod and RGAP for improving immune activity may provide an additional benefit over the use of the two drugs by themselves.Next,the synergistic effect of pidotimod and red ginseng acidic polysaccharide (RGAP) from Panax ginseng C.A.Meyer on humoral immune response was examined by lipopolysaccharide(LPS) and sheep red blood cells(SRBC) in immunosuppressed mice.Combined treatment of pidotimod and RGAP significantly increased the number of plaque-forming cells in spleen in response to both of LPS and SRBC,while treatment individually with either pidotimod or RGAP had no such effect.IgG levels in serum was augmented for secondary responses to SRBC in co-treated mice,but not in mice treated with each drug alone.Microscopic studies revealed conserved architecture of the spleen,thymus,and lymph nodes. GPT and creatinine in serum as indicators of hepatic and renal functions showed no difference compared to control group.These results indicate the combined treatment with pidotimod and RGAP has an immunostimulatory effect in a synergistic manner on antibody response challenged with LPS and SRBC without toxic alterations.Macrophages play a significant role in the regulation of immunological reactions through various functions.In the last chapter,stimulated macrophage functions such as pinocytosis,phagocytosis and respiratory burst were determined as well as expression of iNOS gene and costimulatory molecules.The results indicated the combination of pidotimod and RGAP inhibited the cyclophophamide-induce decrease of uptake of neutral red,phagocytosis with fluorescent beads and production of superoxide anion,which suggests the treatment may be regulate the innate immunity.The expression of CD80 and CD86 were increased by combined treatment of pidotimod and RGAP,which suggests that it may be able to regulate the function of macrophages as an antigen-presenting cell.The iNOS gene expression was increased by RT-PCT, which is consistent with the result before.On the basis of the results obtained in the present study,the present study has demonstrated that the combination of pidotimod and RGAP acts synergistically in enhancing the immunostimulating effect in immunosuppressed mice.It also possesses a potent immunostimulating action on humoral immune system challenged with TD and TI antigen,and activated several parameters of macrophage functions.In view of these data the finding that combined therapy with pidotimod and RGAP in our immunosuppressed model showed good results and in almost all the cases was better than their respective monotherapies.The combination tested here can offer alternative therapies for immunosuppression treatment.