The Regulatory Effect of Si-Jun-Zi-Tang and Its Four Ingredients on The Murine Immune Function

• Main Authors: Liu Chien Chiung, 劉倩君
• Other Authors: Tseng Jerming
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/91749126679791177250

博士 === 國立臺灣師範大學 === 生物研究所 === 91 === Si-Jun-Zi-Tang is a general tonic medicine that has been used in Asian countries for more than a thousand years. It is composed of four major ingredients including Ginseng (Panax ginseng C.A Meyer), Bai-zhu (Atraclylodes macrocephala Koidz), Licorice (Glycyrrhiza uralensis Fisch) and Fu-ling (Poria cocos (Schw.) Wolf). In 1996, our research team had demonstrated that Si-Jun-Zi-Tang was a potential immunoregulatory medicine. Therefore, the research was taken through a series of carefully designed experiments to investigate closely into the mechanism by which the Si-Jun-Zi-Tang modulated the immune function. The reagents used in this study were prepared by boiling the Si-Jun-Zi-Tang and its four major ingredients separately in 50% ethanol. In the primary stage of the experiment, the mice were injected intraperitoneally (i.p.) with the extracts for three consecutive days. Results indicated that injecting the drug all significantly enhanced both IgG and IgA secretion by spleen cells, but IgM secretion was not augmented significantly by Si-Jun-Zi-Tang, Bai-zhu and Fu-ling. In the secondary stage, assayed for production of Th-1 type (IL-2, IFN-g) and Th-2 type (IL-4 and IL-10) cytokines by spleen cells cultured in vitro. Results indicated that treatment with drug all significantly enhanced both cytokine mRNA expression and cytokine secretion by spleen cells. This observation was further supported by showing that the IgG1, IgG2b (mediated by IL-4) and IgG2a (mediated by IFN-g) secretion by spleen cells were increased significantly after the drug treatments. The result also implied that antibodies production by the B-lymphocytes might undergo class-switch. In the third stage, the study was focused on the possible effects of the route and the duration of drug treatment on the Ginseng-mediated immunoregulation. Oral administration of Ginseng extract only enhanced the secretion of IgA, but showed a significantly suppressive effect on IgG and IgM secretion, suggesting that Ginseng might directly stimulate the mucosal-associated lymphoid tissue in gut and augmented IgA production though oral administration. Oral administration of Ginseng extract significantly enhanced Th-1 type cytokine production and IL-10 production. This observation was further supported by showing that the IgG2a secretion by spleen cells, which was induced by IFN-g, were increased significantly after the drug treatments; but IgG1 and IgG2b secretion, which was induced by IL-4, were suppressed. In addition, oral administration of Ginseng significantly increased the cytotoxic activity of natural kill cells (NK cells), suggesting that Ginseng can also induced an innate cell-mediated immune response. However, oral administration of Ginseng extract significantly reduced the percentage composition of CD3+ T-lymphocytes,CD4+8- and CD4-8+ subpopulations. The Ginseng-mediated immunoregulation was also affected by the duration of drug treatment. Long-term (30 days) oral treatment of Ginseng almost failed to modulate both immunoglobulin and cytokine productions, except that the production of IL-10 was significantly induced. Since, the major biological activity of IL-10 is to inhibit the synthesis of lymphokines and monokines. Therefore, long-term oral treatment of Ginseng extract might down-regulate the immune system by increasing IL-10 production. Finally, the effect of long-term oral treatment of Ginseng extract on the ovalbumin (OVA)-induced specific antibody response was studied. During the 30 days of treatment, the mice were primary immunized with OVA at day one and were boosted at day 14. The anti-OVA antibody titer of the mice treated with Ginseng was significantly higher than that of the control group. In conclusion, for the 50% ethanol extract of Ginseng, the dosage ranged from 0.4 g/kg/day to 4 g/kg/day, the short-term oral administration will up-regulate both MALT response and cell-mediated immune response, especially the cytotoxicity of NK cells. However, long-term oral administration will not be able to augment immune response but may have advantage in the antigen-specific antibody response.