Cordyceps sinensis 

Yuh-Chi Kuo¹*, Wei-Jern Tsai¹, Ming-Shi Shiao², Chieh-Fu Chen’ and Ching-Yuang Lin³

‘National Research Institute of Chinese Medicine,

²Lipid Research Laboratory, Department of Medical Research,

³Department of Pediatrics, Veterans General Hospital, Taipei, Taiwan

(Accepted for publication February 28,1996)

Abstract: Effects of various fractions of methanol extracts from fruiting bodies of Cordyceps sinensis on the lymphoproliferative response, natural killer (NK) cell activity, and phytohemagglutiflifl (PHA) stimulated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production on human mononuclear cells (HMNC) were studied. Two of the 1 column fractions (CS-36-39 and CS-48-5 1) significantly inhibited the blastogenesis response (IC50=71.0± 3.0 and 21.7 ± 2.0 ug/ml, respectively), NK cell activity (IC5o = 25.0 ± 2.5 and 12.9 ± 5.8 ug/ml, respectively) and IL-2 production of HMNC stimulated by PHA (IC5o = 9.6 ± 2.3 and 5.5 ± 1.6 ug/ml, respectively). TNF-alpha production in HMNC cultures was also blocked by CS-36-39 and CS-48-51 (1C50 = 2.7 ± 1.0 and 12.5±3.8 ug/ml, respectively). These results indicated that neither CS-36-39 nor CS-48-51 was cytotoxic on HMNC, and that immunosuppressive ingredients are contained in Cordyceps sinensis.

Cordyceps sinensis (C. sinensis), a major parasitic fungus, grows on the larvae of Lepidoptera (Mains, 1958; McEwen, 1963, Kabayasi, 1941). It is one of the best known fungi used in traditional medicine in China (Shimitsu, 1978). Various bioactive components are contained in fungi of the genus Cordyceps. In 1950, the nucleoside derivative-cordycepin was isolated from C. militaris by Cuningham et al. (Cuningham et aI., 1950, Kredich and Guarino, 1961). Reported biological activities of cordycepin include: (a) inhibition of DNA and RNA synthesis (Plageman and Erbe, 1971); (b) enhancement of cell differentiation (Mathew et al., 1989); (c) restructuring of cytoskeleton in cells (Deitchand, 1979, Zieve and Roemer, 1988); (d) inhibition of protein kinase activity (Glazer and Kuo, 1977); (e) antitumor activity on bladder, colon, lung carcinoma as well as fibroblastoma (Hubell et al., 1985); (f) inhibition of the infection and reverse transcriptase activity of human immunodeficiency virus type I (Montefiori et al., 1989; Muller et al., 1991); (g) inhibition of methylation of nucleic acid (Noval-Fernandez and Leory, 1980); and (h) inhibition of chemotaxis and specific proteins synthesis of the macrophage cell line (Aksaniit et al., 1983). In 1983, galactomannan, a polysaccharide isolated from C. cicadae was shown to prevent the growth of sarcoma 180 in mice (Ukai et al., 1983). In addition, polysaccharides purified from C. ophioglossoides have been reported as antitumor agents (Ohmari et al., 1986, Yanada, 1984). Thus, it is suggested that Cordyceps sp. exhibits antitumor, antiviral, and many other biological activities.

In 1989, Shiao et al. identified several compounds including fatty acids, adenosine, ergosteryl-Beta-D-glucopyranoside and 22-dihydroergosteryl-beta-glucopyranoside from the fruiting bodies of C. sinensis. (Shiao eta!., 1989). On the other hand, we have found tumor cell growth inhibitors other than cordycepin and polysaccharides in fruiting bodies extracts of C. sinensis (Kuo eta!., 1994). The present study was initiated to systematically examine and compare the effects of various C. sinensis crude extracts on cell-mediated immune responses.

Natural killer (NK) cells are large granular lymphocytes. They recognize and lyse tumor cells and virally infected cells, and play an important role in immune surveillance (Haller et al., 1977; Harrison and Waner, 1985; Herberman et al., 1975a, l975b; Kuo et al., 1987; Lin et al., 1987). Interleukin-2 (IL-2) is a 15.5 Kd glycoprotein encoded by a gene located in human chromosome 4 (Tanaguchi et al., 1983). IL-2 binds to its receptor, leading to T-cell proliferation, and finally the generation of specific regulatory and effector cells (Smith, 1980, 1984). Tumor necrosis factor-alpha-(TNF-alpha) is a 17 Kd protein that plays essential roles in inflammatory response and antitumor function (Shirai et al., 1985; Wang et al., 1985; Beutler and Ceromi, 1989). TNF-alpha treated T cells show an enhanced proliferative response to IL-2. Both IL-2 and TNF-alpha regulate NK cell activity (Degliantoni et al., 1985; Peters et al., 1986; Smith, 1984). Immune response is a multifaceted process in which all these actions are involved. Changes in any of these activities resulted in the modulation of overall immune response. In the present study, immunomodulatory activity of the methanol extracts of fruiting bodies of C. sinensis were examined through the effects of their various fractions on lymphoproliferation, NK cytotoxicity, IL-2 and TNF-alpha production on human mononuclear cells (HMNC).

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