DOI QR코드

DOI QR Code

Effect of Cordycepin-increased Cordyceps militaris Powder on Tissues Lipid Peroxidation and Antioxidative Activity in Carbon Tetrachloride-induced Hepatic Damage in Rats

Cordycepin이 사염화탄소 유발 간손상 흰쥐의 조직 과산화 지질 농도 및 항산화 활성에 미치는 영향

  • Ahn, Hee-Young (Department of Medical Biosciences, Graduate School, Dong-A University) ;
  • Park, Kyu-Rim (Department of Medical Biosciences, Graduate School, Dong-A University) ;
  • Kim, Yu-Ra (Department of Biotechnology, Dong-A University) ;
  • Cha, Jae-Young (Technical Research Institute, Daesun Distilling Co., Ltd.) ;
  • Cho, Young-Su (Department of Biotechnology, Dong-A University)
  • 안희영 (동아대학교 대학원 의생명과학과) ;
  • 박규림 (동아대학교 대학원 의생명과학과) ;
  • 김유라 (동아대학교 생명공학과) ;
  • 차재영 (대선주조(주)기술연구소) ;
  • 조영수 (동아대학교 생명공학과)
  • Received : 2013.06.07
  • Accepted : 2013.07.25
  • Published : 2013.07.30

Abstract

This study aimed to evaluate the protective effect of cordycepin-increased Cordyceps militaris strain on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and oxidative stress in rats. Male Sprague-Dawley rats were randomly divided into five groups (n=6) based on six dietary categories: normal (N), $CCl_4$ control (C), $CCl_4$ plus Paecilomyces japonica (CPJ) (3%, w/w), $CCl_4$ plus C. militaris (CCM) (3%, w/w), and $CCl_4$ plus cordycepin-increased C. militaris ($CCM{\alpha}$) (3%, w/w). The activities of the liver marker enzymes ALT, AST, and LDH and the levels of lipid peroxidation were increased in the $CCl_4$-treated groups, but these parameters were significantly decreased in the $CCM{\alpha}$ group. The TBARS content in the liver homogenate, microsome, and mitochondrial fractions of the C group was significantly elevated compared with the N group. However, in the $CCl_4$-treated groups, $CCM{\alpha}$ group was significantly lowered in the TBARS levels of hepatic homogenate and microsomal fractions. The C group showed a significant decrease in the levels of plasma and hepatic glutathione, whereas they were significantly increased in the $CCM{\alpha}$ group. Accordingly, cordycepin-increased C. militaris may be an ideal animal model for studying hepatoprotective effects.

눈꽃 동충하초, 번데기 동충하초, Cordycepin 고함유 번데기 동충하초 분말을 식이 중에 각각 3% 수준으로 첨가하여 4주간 흰쥐에 급여한 후, 해부하기 2일 전에 2회 사염화탄소를 복강주사하여 급성 간손상을 일으켜 임상생화학적 특성 및 조직 내 항산화 활성 및 간 조직에 미치는 영향을 검토하였다. 체중 증가량과, 식이 섭취량 및 음료섭취량은 각 실험군 모두 감소하는 경향을 보였다. 간 손상 임상 지표인 AST, ALT, LDH 활성도 각 실험군 모두 유의적으로 감소하였으나, 그 중 Cordycepin 고함유 번데기 동충하초 분말을 투여한 군에서 가장 낮은 활성을 보였다. 각 조직과 혈청의 과산화지질(TBARS)을 측정한 결과 Cordycepin 고함유 번데기 동충하초는 높은 과산화지질 억제작용을 나타내어 조직 내 항산화 물질로 잘 알려진 glutathione농도 또한 모든 조직과 혈청내에서 높은 함량을 보였다. 미네랄 함량 측정결과 지방의 산화를 촉진하는 비헴철과 항산화 성분인 아연이 정상수준까지 회복되는 경향을 보였다. 이상의 실험결과 Cordycepin 고함유 번데기 동충하초는 사염화탄소로 유발된 간 독성을 저하시키며 혈청과 간지질 대사를 개선하는 효과가 있는 것으로 사료되며 향후 간 기능 개선과 지질대사 개선효능을 가지는 건강식품 개발의 소재로 활용될 가능성이 높은 것으로 판단되어진다.

Keywords

References

  1. A.O.A.C. 1975. Official methods of analysis. 12th ed., Association of official analytical chemists. Washington DC, USA.
  2. Beutler, E., Duron, O. and Kelly, B. M. 1963. Improved method for the determination of blood glutathione. J Lab Clin Med 61, 882-888.
  3. Borek, C. 2001. Antioxidant health effects of aged garlic extract. J Nutr 131, 1010-1015. https://doi.org/10.1093/jn/131.3.1010S
  4. Brattin, W. J., Glende E. A. J. and Recknagel, R. O. 1985. Pathological mechanisms in carbon tetrachloride hepatotoxicity. J Free Radic Biol Med 1, 27-38. https://doi.org/10.1016/0748-5514(85)90026-1
  5. Buang, Y., Wang, Y. M., Cha, J. Y., Nagao, K. and Yanagita, T. 2005. Dietary phosphatidylcholine alleviates fatty liver induced by orotic acid. Nutrition 21, 867-873. https://doi.org/10.1016/j.nut.2004.11.019
  6. Cha, J. Y., Ahn, H. Y., Heo, S. J., Park, S. H., Jeong, Y. K. and Cho, Y. S. 2011. Improvement effect of cordycepin- enriched Cordyceps militaris JLM 0636 powder against orotic acid-induced fatty liver in rats. J Life Sci 21, 1274-1280. https://doi.org/10.5352/JLS.2011.21.9.1274
  7. Chiba, H., Takasaki, M., Masuyama, R., Uehara, M., Kanke, Y., Suzuki, K. and Goto, S. 1998. Time course of change in hepatic lipid peroxide level in iron-deficient rats. J Jpn Soc Nutr Food Sci 51, 201-206. https://doi.org/10.4327/jsnfs.51.201
  8. Cho, H. J., Cho, J. Y., Rhee, M. H., Kim, H. S., Lee, H. S., and Park, H. J. 2007. Inhibitory effects of cordycepin (3'-deoxyadenosine), a component of Cordyceps militaris, on human platelet aggregation induced by thapsigargin. J Microbiol Biotechnol 17, 1134-1138.
  9. Diehl, A. M. 1993. Effects of alcohol on liver regeneration. Alcohol Health Res W 17, 279-283.
  10. Duncan, D. B. 1957. Multiple range test for correlated and heteroscedastic means. Biometrics 13, 164-176. https://doi.org/10.2307/2527799
  11. Guo, P., Kai, Q., Gao, J., Lian, Z. Q., Wu, C. M., Wu, C. A. and Zhu, H. B. 2010. Cordycepin prevents hyperlipidemia in hamsters fed a high-fat diet via activation of AMP-activated protein kinase. J Pharmacol Sci 113, 395-403. https://doi.org/10.1254/jphs.10041FP
  12. Ha, T. Y., Cho, I. J. and Lee, H. Y. 2001. Effect of Cassia tora ethanol extracts on carbontetrachloride-induced liver injury in rats. Korea J Food Sci Technol 33, 789-794.
  13. Hidaka, I., Hino, K., Korenaga, M., Gondo, T., Nishina, S., Ando, M., Okuda, M. and Sakaida, I. 2007. Stronger Neo-Minophagen C, a glycyrrhizin-containing preparation, protects liver against carbon tetrachloride-induced oxidative stress in transgenic mice expressing the hepatitis C virus polyprotein. Liver Int 27, 845-853 https://doi.org/10.1111/j.1478-3231.2007.01492.x
  14. Illana, E. C. 2007. Cordyceps sinensis, a fungi used in the Chinese traditional medicine. Rev Iberoam Micol 24, 259-262. https://doi.org/10.1016/S1130-1406(07)70052-9
  15. Ji, D. B., Ye, J., Li, C. L., Wang, Y. H., Zhao, J. and Cai, S. Q. 2009. Antiaging effect of Cordyceps sinensis extract. Phytother Res 23, 116-122. https://doi.org/10.1002/ptr.2576
  16. Jin, Y. X., Yoo, Y. S., Han, E. K., Kang, I. J. and Chung, C. K. 2008. Artemisia capillaries and Paecilomyces japonica simulate lipid metabolism and reduce hepatotoxicity induced by carbon tetrachloride in rats. J Korean Soc Food Sci Nutr 37, 548-554. https://doi.org/10.3746/jkfn.2008.37.5.548
  17. Jo, W. S., Nam, B. H., Oh, S. J., Choi, Y. J. and Kang, E. Y. 2008. Hepatic protective effect and single-dose toxicity study of water extract of Cordyceps militaris grown upon Protaetia dreujtarsis. Korean J Food Sci Technol 40, 106-110.
  18. Johansson, I. and Ingelman-Sundberg, M. 1985. Carbon tetrachloride-induced lipid peroxidation dependent on an ethanol-inducible form of rabbit liver microsomal cytochrome P-450. FEBS Lett 183, 265-269. https://doi.org/10.1016/0014-5793(85)80790-0
  19. Jung, M. E., Ham, S. S., Nam, S. M., Kang, I. J., Kim, S. J. and Chung, C. K. 2001. Biochemical and histological effects of Phellinus linteus methanol extract on liver lipid metabolism of rats fed $CCl_{4}$ and high fat. J Korean Soc Food Sci Nutr 30, 331-337.
  20. Kaplowitz, N., Aw, T. Y. and Ookhtens, M. 1985. The regulation of hepatic glutathione. Annu Rev Pharmacol Toxicol 25, 715-744. https://doi.org/10.1146/annurev.pa.25.040185.003435
  21. Kim, S. Y., Kim, H. P., Lee, M. K. and Byun, S. J. 1993. The effect of betain on the $CCl_4$-induced hepatotoxicity in rats. Yakhak Hoeji 37, 538-541
  22. Kirchgessner, M., Roth, H. P. and Weigand, E. 1976. In trace elements in human health and disease. Academic Press New York 189.
  23. Koh, J. B. 2002. Effect of Mycelium of Cordyceps militaris on growth, lipid metabolism and protein levels in male rats. J Korean Soc Food Sci Nutr 31, 685-690. https://doi.org/10.3746/jkfn.2002.31.4.685
  24. Koh, J. B. and Choi, M. A. 2003. Effect of Paecilomyes japonica on lipid metabolism in rats fed high fat diet. J Korean Soc Food Sci Nutr 32, 238-243. https://doi.org/10.3746/jkfn.2003.32.2.238
  25. Lee, E. W., He, P., Kawagishi, H. and Sugiyama, K. 2000. Suppression of D-galactosamine-induced liver injury by mushroom in rats. Biosci Biotech Biochem 64, 2001-2002. https://doi.org/10.1271/bbb.64.2001
  26. Lee, J. S., Kwon, J. S., Won, D. P., Lee, J. H., Lee, K. E., Lee, S. Y. and Hong, E. K. 2010. Study of macrophage activation and structural characteristics of purified polysaccharide from the fruiting body of Cordyceps militaris. J Microbiol Biotechnol 20, 1053-1060. https://doi.org/10.4014/jmb.0910.10022
  27. Li, S. P., Zhang, G. H., Zeng, Q., Huang, Z. G., Wang, Y. T., Dong, T. T. and Tsim, K. W. 2006. Hypoglycemic activity of polysaccharide, with antioxidation, isolated from cultured Cordyceps mycelia. Phytomedicine 13, 428-433. https://doi.org/10.1016/j.phymed.2005.02.002
  28. Manninen, V., Tenkanen, L., Koskinen, P., Huttunen, J. K., Manntari, M., Heinonen, O. P. and Frick, M. H. 1992. Triglycerides and LDL-cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study. Circulation 85, 37-45. https://doi.org/10.1161/01.CIR.85.1.37
  29. Noll, T. and Groot, H. 1984. The critical steady state hypoxic conditions in carbon tetrachloride induced lipid peroxidation in rat liver microsomes. Biochem Biophys Acta 795, 356-361. https://doi.org/10.1016/0005-2760(84)90086-9
  30. Plaa, G. L. and Witschi, H. 1976. Chemicals, drugs, and lipid peroxidation. Annu Rev Pharmacol Toxicol 16, 125-141. https://doi.org/10.1146/annurev.pa.16.040176.001013
  31. Shon, M. H., Cha, J. Y., Lee, C. H., Park, S. H. and Cho, Y. S. 2007. Protective effect of administrated glutathione-enriched Saccharomyces cerevisiae FF-8 against carbon tetrachloride ($CCl_4$)-induced hepatotoxicity and oxidative stress in rats. Food Sci Biochenol 16, 967-974.
  32. Sugiyama, Y. and Yamamoto, K. 1998. The protective effect of glutathione-enriched yeast extract on acetaminophen-induced liver damage in rats. J Jpn Soc Nutr Food 51, 189-193. https://doi.org/10.4327/jsnfs.51.189
  33. Takeda, Y., Ichihara, A., Tanioka, H. and Inoue, H. 1964. The biochemistry of animal cells. I. The effect of corticosteroids on leakage of enzymes from dispersed rat liver cells. J Biol Chem 239, 3590-3596.