DOI QR코드

DOI QR Code

Immunomodulatory Activities of Ethanol Extract of Cordyceps militaris in Immunocompromised Mice

밀리타리스 동충하초(Cordyceps militaris) 에탄올 추출물의 면역억제 마우스 면역활성에 미치는 영향

  • Received : 2012.01.06
  • Accepted : 2012.02.21
  • Published : 2012.04.30

Abstract

In order to determine the functional benefits of $Cordyceps$ $militaris$ in the immune system, we examined the immunomodulatory activities of $Cordyceps$ $militaris$ in an immunocompromised C57BL/6 mice model. Mice were injected intraperitoneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 3% hydroxypropylmethylcellulose or 30, 100, and 300 mg/kg of 50% ethanol extract of $Cordyceps$ $militaris$ (CM 30, CM 100, and CM 300, respectively) for 12 days. Mice treated with CM displayed significantly increased splenocyte proliferation and natural killer cell activity compared to immunosuppressed control mice (p<0.05). The spleen cells isolated from mice treated with CM also displayed increased production of Th1 cytokines, including IL-2, IL-12, IFN-${\gamma}$ and TNF-${\alpha}$, suggesting enhanced cellular immunity in response to CM. However, CM had no significant effect on the production of IL-4 and IL-10. These results indicate that $Cordyceps$ $militaris$ enhances immune function by promoting immune cell proliferation and Th1 cytokine production.

본 연구에서는 면역억제 동물모델에서 밀리타리스 동충하초 50% 에탄올 추출물의 면역력 증강 기능을 평가하였다. 이를 위하여 C57BL/6 마우스에 cyclophosphamide를 2회 복강주사 하여 면역력을 억제한 후, 밀리타리스 동충하초 추출물을 30, 100, 300 mg/kg 용량으로 12일간 경구투여 하였다. 마우스를 희생하여 몸무게 및 면역장기 무게, 비장세포의 증식, 비장세포의 cytokine 분비능, NK 세포 활성을 측정하였다. 그 결과, cyclophosphamide 투여에 의한 면역억제는 마우스의 몸무게와 간의 무게에 영향을 주지 않았으나 흉선의 무게는 감소시켰고 비장의 무게는 증가시켰다. 밀리타리스 동충하초 추출물 투여는 마우스의 몸무게 및 면역장기 무게에 영향을 주지 않았다. Cyclophosphamide 투여는 비장세포의 증식능을 감소시켰으며 밀리타리스 동충하초 추출물은 용량 의존적으로 비장세포 증식을 증가시켜 실험에 사용한 전 용량에서 비장세포의 유의적인 증식효과를 보였다. 비장세포의 cytokine 분비능을 측정한 결과, 밀리타리스 동충하초 추출물 투여는 IL-2, IL-12, IFN-${\gamma}$, TNF-${\alpha}$ 같은 Th1 cytokine의 분비를 대조군에 비해 유의적으로 증가시켰으나, IL-4와 IL-10 같은 Th2 cytokine의 분비에는 영향을 미치지 않았다. 또한 cyclophosphamide는 NK 세포의 활성을 정상군에 비하여 유의적으로 감소시켰으며, 밀리타리스 동충하초 추출물 투여는 cyclophosphamide에 의해 저하된 NK 세포 활성을 현저하게 증가시켰다. 이상의 결과를 종합해 볼 때, 밀리타리스 동충하초는 면역력이 억제된 상황에서 면역력을 증강시키며, 이러한 면역력 증강 효과는 체액성 면역보다 세포성 면역력 증강에 기인하는 것으로 보인다.

Keywords

References

  1. Sung JM, Lee HK, Choi YS, Kim YY, Kim SH, Sung GH. 1997. Distribution and taxonomy of entomopathogenic fungal species from Korea. Kor J Mycol 25: 239-252.
  2. Sung GH, Hywel-Jones NL, Sung JM, Luangsa-Ard JJ, Shrestha B, Spatafora JW. 2007. Phylogenetic classification of Cordyceps and the clavicipitaceous fungi. Stud Mycol 57: 5-59. https://doi.org/10.3114/sim.2007.57.01
  3. Ying J. 1987. Icons of medicinal mushroom from China. Beijing Science Press, Beijing, China. p 151-155.
  4. Mizuno T. 1999. Medicinal effects and utilization of Cordyceps (Fr.) Link (Ascomycetes) and Isaria Fr. (Mitosporic fungi) Chinese caterpillar fungi, "Tochukaso" (review). Intl J Med Mushroom 1: 251-261. https://doi.org/10.1615/IntJMedMushrooms.v1.i3.80
  5. Song CH, Jeon YJ, Yang BK, Ra KS, Sung JM. 1998. Anticomplementary activity of exo-polymers produced from submerged mycelial cultures of higher fungi with particular reference to Cordyceps militaris. J Microbiol Biotechnol 8: 536-539.
  6. Ng TB, Wang HX. 2005. Pharmacological actions of Cordyceps, a prized folk medicine. J Pharm Pharmacol 57: 1509-1519. https://doi.org/10.1211/jpp.57.12.0001
  7. Yu R, Song L, Zhao Y, Bin W, Wang L, Zhang H, Wu Y, Ye W, Yao X. 2004. Isolation and biological properties of polysaccharide CPS-1 from cultured Cordyceps militaris. Fitoterapia 75: 465-472. https://doi.org/10.1016/j.fitote.2004.04.003
  8. Won SY, Park EH. 2005. Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J Ethnopharm 96: 555-561. https://doi.org/10.1016/j.jep.2004.10.009
  9. Yu RM, Yang W, Song LY, Yan CY, Zhang Z, Zhao Y. 2007. Structural characterization and antioxidant activity of a polysaccharide from the fruiting bodies of cultured Cordyceps militaris. Carbohydrate Polym 70: 430-436. https://doi.org/10.1016/j.carbpol.2007.05.005
  10. Chen C, Luo SS, Li Y, Sun YJ, Zhang CK. 2004. Study on antioxidant activity of three Cordyceps sp. by chemiluminescence. Shanghai J Trad Chinese Med 38: 53-55.
  11. Lee H, Lee Y, Park T. 2004. Tumor growth inhibitory and immunomodulatory activities of Cordyceps militaris water extracts in ICR mice bearing sarcoma-180 solid tumor. J Korean Soc Food Sci Nutr 33: 59-65. https://doi.org/10.3746/jkfn.2004.33.1.059
  12. Liu J, Yang S, Yang X, Chen Z, Li J. 1997. Anticarcinogenic effect and hormonal effect of Cordyceps militaris. Zhongguo Yao Za Zhi 22: 111-113.
  13. Johns DG, Adamson RH. 1976. Enhancement of the biological activity of cordycepin (3'-deoxyadenosine) by the adenosine deaminase inhibitor 2'-deoxycoformycin. Biochem Pharmacol 25: 1441-1444. https://doi.org/10.1016/0006-2952(76)90121-0
  14. Muller WE, Seibert G, Beyer R, Breter HJ, Maidhof A, Zahn RK. 1977. Effects of cordycepin on nucleic acid metabolism in L5178Y cells and on nucleic acid-synthesizing enzymes. Cancer Res 37: 3824-3833.
  15. Kodama EN, McCaffrey RP, Yusa K, Mitsuya H. 2000. Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT+) leukemic cells. Biochem Pharm 59: 273-281. https://doi.org/10.1016/S0006-2952(99)00325-1
  16. Lin YW, Chiang BH. 2008. Anti-tumor activity of the fermentation broth of Cordyceps militaris cultured in the medium of radix astragali. Proc Biochim 43: 244-250. https://doi.org/10.1016/j.procbio.2007.11.020
  17. Mao XB, Zhong JJ. 2006. Significant effect of $NH_4^+$ on cordycepin production by submerged cultivation of medicinal mushroom Cordyceps militaris. Enzyme Microb Technol 38: 343-350. https://doi.org/10.1016/j.enzmictec.2004.10.010
  18. Cunningham KG. 1951. Cordycepin, a metabolic product from cultures of Cordyceps militaris (Linn.) Link. Part I. Isolation and characterization. J Chem Soc 1: 2299-3200.
  19. Muller WE, Weiler BE, Charubala R, Pfleiderer W, Leserman L, Sobol RW, Suhadolnik RJ, Schröder HC. 1991. Cordycepin analogues of 2'5'-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase. Biochemistry 30: 2027-2033. https://doi.org/10.1021/bi00222a004
  20. Mishell BB, Shiigi SM. 1980. Selected methods in cellular immunology. 1st ed. WHFreeman and Co., San Francisco, CA, USA. p 4-27.
  21. Kim JW, Kim C. 2005. Inhibition of LPS-induced NO production by taurine chloramine in macrophages is mediated through Ras-ERK-NF${\kappa}B$. Biochem Pharmacol 70: 1352-1360. https://doi.org/10.1016/j.bcp.2005.08.006
  22. Miyauchi A, Hiramine C, Tanaka S, Hojo K. 1990. Differential effects of a single dose of cyclophosphamide on T cell subsets of the thymus and spleen in mice: flow cytofluorometry analysis. Tohoku J Exp Med 162: 147-167. https://doi.org/10.1620/tjem.162.147
  23. Joyce RA, Hartmann O, Chervenick PA. 1979. Splenic granulopoiesis in mice following administration of cyclophosphamide Cancer Res 39: 215-218.
  24. Zhang J, Yu Y, Zhang Z, Ding Y, Dai X, Li Y. 2011. Effect of polysaccharide from cultured Cordyceps sinensis on immune function and anti-oxidation activity of mice exposed to $^{60}Co$. Int Immunopharmacol 11: 2251-2257. https://doi.org/10.1016/j.intimp.2011.09.019
  25. Siu KM, Mak DH, Chiu PY, Poon MK, Du Y, Ko KM. 2004. Pharmacological basis of 'Yin-nourishing' and 'Yang-invigorating' actions of Cordyceps, a Chinese tonifying herb. Life Sci 76: 385-395. https://doi.org/10.1016/j.lfs.2004.07.014
  26. Ha JW, Yoo HS, Shin JW, Cho JH, Lee NH, Yoon DH, Lee YW, Son CG, Cho CK. 2006. Effects of Cordyceps militaris extract on tumor immunity. Kor J Ori Med 27: 12-29.
  27. Kim GY, Ko WS, Lee JY, Lee JO, Ryu CH, Choi BT, Park YM, Jeong YK, Lee KJ, Choi KS, Heo MS, Choi YH. 2006. Water extract of Cordyceps militaris enhances maturation of murine bone marrow-derived dendritic cells in vitro. Biol Pharm Bull 29: 354-360. https://doi.org/10.1248/bpb.29.354
  28. Kuo YC, Tsai WJ, Shiao MS, Chen CF, Lin CY. 1996. Cordyceps sinensis as an immunomodulatory agent. Am J Chin Med 24: 111-125. https://doi.org/10.1142/S0192415X96000165

Cited by

  1. Effects of LED on the growth of P. tenuipes vol.52, pp.1, 2014, https://doi.org/10.7852/jses.2014.52.1.59
  2. Cordyceps militarisEnhances Cell-Mediated Immunity in Healthy Korean Men vol.18, pp.10, 2015, https://doi.org/10.1089/jmf.2014.3350
  3. Effect of silkworm varieties on Paecilomyces tenuipes culture vol.53, pp.2, 2015, https://doi.org/10.7852/jses.2015.53.2.87
  4. Effect of Alpina Officinarum Ethanol Extract on Immunoregulatory Activities in the Mice vol.24, pp.1, 2014, https://doi.org/10.5352/JLS.2014.24.1.61
  5. Immuno-stimulating Activities of Skipjack Tuna Katsuwonus pelamis Cooking Juice Concentrates on Mouse Macrophages and Spleen Cells vol.47, pp.6, 2014, https://doi.org/10.5657/KFAS.2014.0776
  6. Effects of Agaricus blazei Murill Water Extract on Immune Response in BALB/c Mice vol.44, pp.11, 2015, https://doi.org/10.3746/jkfn.2015.44.11.1629
  7. in splenocytes and cyclophosphamide-induced immunosuppressed mice vol.32, pp.1, 2017, https://doi.org/10.1002/ptr.5960
  8. 한국에서 개발된 곤충유래 약용버섯인 누에동충하초의 생산기술개발 및 약리학적 특성 vol.27, pp.2, 2012, https://doi.org/10.5352/jls.2017.27.2.247
  9. 발효 미생물에 따른 누에동충하초 발효산물의 특성 vol.15, pp.4, 2012, https://doi.org/10.14480/jm.2017.15.4.237
  10. Preventive Effect of the Herbal Preparation, HemoHIM, on Cisplatin-Induced Immune Suppression vol.2019, pp.None, 2012, https://doi.org/10.1155/2019/3494806