Effects of Cordyceps on the immune system have been reported; however, the experimental results are controversial and show that Cordyceps possesses both potentiation and/or inhibition effects on the immunoresponse. Thus, it is assumed that Cordyceps is a bidirectional modulator of the immune system.
The spleen weight of mice was significantly increased by oral administration of water extract derived from Cordyceps; the extract increased the synthesis of DNA and protein, which promoted the proliferation of spleen lymphocytes. The active ingredients that caused the elevation of spleen weight subsequently were identified and partially purified from the fruiting body of Cordyceps.
The immune system in tumor-bearing mice was greatly enhanced by treatment with Cordyceps. C57BL/6 mice implanted subcutaneously with EL-4 lymphoma cells were employed as the experimental targets. Oral administration of the extract led to a reduction of tumor size in the tumor-bearing mice and prolonged the survival rate of the host. Phagocytic activity of macrophages was decreased in the tumor-bearing mice treated with cyclo-phophamide (100 mg/kg); however, administration of Cordyceps extract restored the activity to higher than the normal level (35).
In animal studies, Cordyceps was shown to stimulate the function of mononuclear phagocytes and the expansion of adhesion cells in the abdominal cavity, phagocytes in the spleen, and Kupffer's cells in the liver (36). A polysaccharide with a size of ~43 kDa, namely CS-81002, was purified from the polysaccharide-enriched cultured medium, where the Cordyceps was fermented. CS-81002, when injected into the mice at a dosage of 5 mg/kg, stimulated the function of phagocytes; however, CS-81002 did not increase the number of plaque-forming cells in the spleen. In addition, CS-81002 could be hydrolyzed by acid to smaller molecules and fewer branches; the size of hydrolyzed molecules ranged from 12 to 41 kDa depending on the acid concentration. Higher molecular weight of hydrolyzed CS-81002 retained the immunoactivity, while the smallest molecule at 12 kDa lost the activity completely (37). Moreover, the function of Kupffer's cell is stimulated by Cordyceps. Rats were administered daily the water extract derived from Cordyceps p.o. at a dose of 200 mg/kg for 25 days until the day before the injection of colloidal carbon. According to the rate of carbon clearance in the blood, the Cordyceps-treated rats showed a shorter half-life of 36% than that of the control (38).
In contrast to the above-mentioned different lines of evidence, Cordy-ceps was shown to suppress immunity function. In cultured T lymphocytes, the application of either natural or cultured Cordyceps onto the cultures inhibited the lymphocyte blastogenesis stimulated by concanavalin A (Con A), and that effect was in a dose-dependent manner. Cultured Cordyceps also significantly inhibited E-rosette formation in humans and prolonged the survival of skin allografts and cardiac tissue transplantation in mice (39,40). Systemic lupus erythematosus is an important autoimmune disease, characterized by the presence of multiple autoantibodies in serum, of which antinuclear antibodies are the predominant species and anti-dsDNA antibodies are the disease-specific species. Female NZB/NZW F1 mice, a typical lupus animal model, were fed with Cordyceps at dosages of 0.025, 0.05, and 0.10 g/day from the time they were 6 weeks old. Mice treated with C. sinensis at 0.1 g/day had a longer survival time than controls. After a few months of Cordyceps treatment, the level of antinuclear antibodies remained the same as that of the controls; however, the titer of anti-dsDNA antibodies was reduced
(41). Furthermore, fractions of methanol extracts from the fruiting bodies of Cordyceps had positive effects on the lymphoproliferative response, natural killer cell activity, and phytohemagglutinin (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-a (TNF-a) production on human mononuclear cells. Further characterization of the fractions indicated that 2 of the 15 isolated fractions (CS-36-39 and CS-48-51) significantly inhibited the blasto-genesisresponse(IC5o,71.0 ± 3.0and21.7 ± 2.0Ag/mL,respectively),natural killer cell activity (IC50, 25.0 ± 2.5 and 12.9 ± 5.8 Ag/mL, respectively), and IL-2 production in PHA-treated human mononuclear cells (IC50, 9.6 ± 2.3 and 5.5 ± 1.6 Ag/mL, respectively). Moreover, the production of TNF-a in human mononuclear cells was blocked by CS-36-39 and CS-48-51 (IC50,2.7 ± 1.0 and 12.5 ± 3.8 Ag/mL, respectively). Neither CS-36-39 nor CS-48-51 had a cytotoxic effect on mononuclear cells in culture (42).
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