DOI QR코드

DOI QR Code

Anti-Obesity Activity, Anti-Cancer Activity and Single Oral Dose Toxicity of Inonotus xeranticus Extracts

기와층버섯 추출물의 항비만활성, 항암활성 및 단회경구독성시험

  • Kang, Eun-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Lee, In-Kyoung (Korea Research Institute of Bioscience and Biotechnology) ;
  • Hwang, Mi-Hyun (College of Veterinary Medicine, Kyungpook National University) ;
  • Choi, Jae-Young (College of Veterinary Medicine, Kyungpook National University) ;
  • Chang, Zhi-Qiang (College of Veterinary Medicine, Kyungpook National University) ;
  • Rhee, Man-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Yun, Bong-Sik (Korea Research Institute of Bioscience and Biotechnology) ;
  • Jiang, Cheng-Zhe (Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences & Peking Union Medica College) ;
  • Kim, Kil-Soo (College of Veterinary Medicine, Kyungpook National University) ;
  • Park, Seung-Chun (College of Veterinary Medicine, Kyungpook National University)
  • Published : 2007.09.30

Abstract

In this study, we investigated the in vitro anti-obesity, anti-cancer activity and single oral dose toxicity of Inonotus xeranticus extracted by methanol (INXM) or ethyl acetate (INXE). In order to investigate anti-obestity effect of Inonotus xeranticus extracts, the 3T3-L1 cells were treated with these extracts at various concentrations(1, 10, 100 and $300{\mu}g/ml$). It was observed that 3T3-L1 cells treated with $100{\mu}g/ml$ of Inonotus obliquus ethyl acetate extract (INOE), INXM and INXE, in the absence of differentiation cocktail (0.5mM isobutylmethylxanthine (IBMX) $1{\mu}M$ dexamethasone, $1{\mu}M$ insulin), differentiated at a rate of 78.5, 80.9, and 76.4% respectively. Differentiation rates of 86.6% and 83.4% were observed in 3T3-L1 cells which were treated with differentiation cocktail at $100{\mu}g/ml$ of INXM and INXE, respectively. The anti-cancer effect of Inonotus xeranticus extracts was investigated using a method of sulforhodamine B in sarcoma 180 cell line. The cells were treated with these extracts (1, 10, 100 and $300{\mu}g/ml$) for 48 hours. The growth of cells which were treated with $300{\mu}g/ml$ of INXM was inhibited by 80.1%. The growth of sarcoma 180 cells which were treated with 100 and $300{\mu}g/ml$ of INXE was inhibited by 74.7% and 64.5%, respectively. In single oral dose toxicity study, no differences were observed between control and treated groups in clinical signs, body weight gains, and feed and water consumptions. The results indicated that Inonotus xeranticus extracts did not show any toxic effects at 2,000mg/kg in mice, and the $LD_{50}$ of these extracts was found to be higher than 2,000 mg/kg in this experiment. From the above results, Inonotus xeranticus methanol and ethyl acetate extracts might have useful clinical applications in the management of cancer and obesity and may also be useful as a medicinal food.

Keywords

References

  1. Bagchi, A., Fridman, A., Holder, D.J., Doebber, T.W., Berger, J., Elbrecht, A., Moller, D.E. and Zhang, B.B. (2002). Gene expression profile of adipocyte differentiation and its regulation by peroxisome proliferation-activated receptorgamma agonists. Endocrinology, 143, 2106-2118 https://doi.org/10.1210/en.143.6.2106
  2. Bianchini, F., Kaaks, R. and Vainio, H. (2002). Overweight, obesity, and cancer risk. Lancet Oncol., 3, 565–574 https://doi.org/10.1016/S1470-2045(02)00850-1
  3. Byun, B.H. (2005). Effects of Inonotus obliquus exthanol extract on cytokine expression in raw 267.4 cell. Kor. J. Herbology, 20, 55-60
  4. Cha, J.Y., Jeon, B.S., Moon, J.C., Yoo, J.H. and Cho, Y.S. (2004). Cytotoxic effect of Inonotus obliquus composition in HCT-15 human colon cancer cells and AGS Gastric cancer cells. J. Kor. Soc. Food Sci. Nutr., 33, 633-640 https://doi.org/10.3746/jkfn.2004.33.4.633
  5. Chen, K.C., Peng, C.C., Peng, R.Y., Su, C.H., Chiang, H.S., Yan, J.H. and Hsieh-Li, H.M. (2007). Unique formosan mushroom antrodia camphorata differentially inhibits androgen-responsive LNCaP and -independent PC-3 prostate cancer cells. Nutr Cancer, 57, 111-121 https://doi.org/10.1080/01635580701268360
  6. Choi, J.H., Park, S.H., Kim, D.I., Kim, J.M., Kim, C.M. and Kim, G.P. (2001). Effects of edible Lentinus tuber-regium on the obesity and lipid matabolism of SD rats. Kor. J. Mycol., 2, 47-51
  7. Ham, S.S., Oh, S.W., Kim, Y.K., Shin, K.S., Chang, H.Y. and Chung, G.H. (2003a). Antioxidant and genotoxic inhibition activity of ethanol extract from the Inonotus obliquus. J. Kor. Soc. Food Sci. Nutr., 32, 1071-1075 https://doi.org/10.3746/jkfn.2003.32.7.1071
  8. Ham, S.S., Oh, S.W., Kim, Y.K., Shin, K.S., Chang, H.Y. and Chung, G.H. (2003b). Antimutagenic and cytotoxic effects of ethanol extract from the Inonotus obliquus. J. Kor. Soc. Food Sci. Nutr., 32, 1088-1094 https://doi.org/10.3746/jkfn.2003.32.7.1088
  9. Huo, H., Guo, X., Hong, S., Jiang, M., Liu, X. and Liao, K. (2003). Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. J. Biol. Chem., 278, 11561- 11569 https://doi.org/10.1074/jbc.M211785200
  10. Hwang, Y.J., Noh, G.W. and Kim, S.H. (2003). Effect of Inonotus obliquos extracts on proliferation and Caspase-3 activity in human gastro-intestinal cancer cell lines. Kor. Nutr. Sci., 36, 18-23
  11. Jeon, B.S., Park, J.W., Kim, B.K., Kim, H.K., Jung, T.S., Hahm, J.R., Kim, D.R., Cho, Y.S. and Cha, J.Y. (2005). Fermented mushroom milk-supplemented dietary fibre prevents the onset of obesity and hypertriglyceridaemia in Otsuka Long-Evans Tokushima fatty rats. Diabetes Obes. Metab., 7, 709-715 https://doi.org/10.1111/j.1463-1326.2005.00456.x
  12. Ju, Y.S. and Ko, B.S. (2002). Natural products, organic chemistry: Screening of insulin - like substances from traditional herbs of diabetes prescrlption in donguibogam. J. Korean Soc. Agric. Chem. Biotechnol., 45, 42-46
  13. Kaaks, E. Lukanova, A. and Kurzer, M.S. (2002). Obesity, endogenous hormones, and endometrial cancer risk: A synthetic review. Cancer Epidem. Biomar., 11, 1531-1543
  14. Kang, K.J. and Kwon, S.Y. (2003). effects of wax gourd extracts of adipocyte differentiation and uncoupling protein genes (ucps) expression in 3T3-L1 preadipocytes. Nutritional Sciences, 6, 148-154
  15. Key, T.G., Appleby, P.N. and Reeves, G.K. (2003). Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J. Natl. Cancer Inst., 95, 1218- 1226 https://doi.org/10.1093/jnci/djg022
  16. Kim, H.M., Han, S.B., Kim, M.S., Kang, J.S., Oh, G.T. and Hong, D.H. (1996): Efficient fixation procedure of human leukemia cells in sulforhodamine B cytotoxicity assay. J. Pharmacol. Toxicol. Methods, 36, 163-169 https://doi.org/10.1016/S1056-8719(96)00113-X
  17. Kim, I.H. and Nam, T.J. (2004). The effects of polymannuronates on leptin in 3T3-L1 adipocytes. J. Kor. Fish. Soc., 37, 372-379
  18. Ko, B.S., Kim, H.K. and Park, S.M. (2002). Natural Products, Organic Chemistry: Insulin Sensitizing And Insulin - like Effects of Water Extracts from Kalopanax pictus NAKAI in 3T3-L1 Adipocyte. J. Korean Soc. Agric. Chem. Biotechnol., 45, 42-46
  19. Ko, B.S., Park, S.K., Choi, S.B., Jun, D.W., Jang, J.S. and Park, S.M. (2004). Hypoglycemic effects of crude extracts of prunus mume. J. Kor. Soc. Food Sci. Nutr., 33, 951- 957 https://doi.org/10.3746/jkfn.2004.33.6.951
  20. Kobori, M., Yoshida, M., Ohnishi-Kameyama, M. and Shinmoto, H. (2007). Ergosterol peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7 macrophages and growth of HT29 colon adenocarcinoma cells. Br. J. Pharmacol., 150, 209-219 https://doi.org/10.1038/sj.bjp.0706972
  21. Koh, J.B. and Lee, C.U. (2005). Effect of Pleurotus eryngii on lipid metabolism in rats fed high fat diet. J. Kor. Soc. Food Sci. Nutr., 34, 626-631 https://doi.org/10.3746/jkfn.2005.34.5.626
  22. Kwoen, D.J., Youn, S.J., Cho, J.G., Choi, U.K. and Kang. S.C. (2006). Antioxidant activities and biological properties of phellinus linteus extracts according to different extraction methods. J. Kor. Soc. Appl. Biol. Chem., 49, 91-96
  23. Lee, I.K., Jung, J.Y., Seok, S.J., Kim, W.G. and Yun, B.S. (2006). Free radical scavengers from the medicinal mushroom Inonotus xeranticus and their proposed biogenesis. Bioorganic & Medicinal Chemistry Letters, 16, 5621-5624 https://doi.org/10.1016/j.bmcl.2006.08.016
  24. Nakata, T., Yamada, T., Taji, S., Ohishi, H., Wada, S.I., Tokuda, H., Sakuma, K. and Tanaka, R. (2007). Structure determination of inonotsuoxides A and B and in vivo antitumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus. Bioorganic & Medicinal Chemistry, 15, 257-264 https://doi.org/10.1016/j.bmc.2006.09.064
  25. OECD (2000): Guidlines for the testing of Chemicals Revised Draft Guideline 423: Acute oral toxicity
  26. Park, S.M., Jun, D.W., Park, C.H., Jang, J.S., Park, S.K., Ko, B.S., Kim, B.J. and Choi, S.B. (2004). Hypoglycemic effects of crude extracts of moutan radicis cortex. Kor. J. Food Sci. Technol., 36, 472-477
  27. Sarangi, I., Ghosh, D., Bhutia, S.K., Mallick, S.K. and Maiti, T.K. (2006). Anti-tumor and immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans. Int. Immunopharmacol., 6, 1287-1297 https://doi.org/10.1016/j.intimp.2006.04.002
  28. Song, H.S., Lee, Y.J., Kim, S.K., Moon, W.K., Kim, D.W., Kim, Y.S. and Moon, K.Y. (2004). Downregulatory effect of AGI-1120 ($\alpha$-glucosidase inhibitor) and Chaga mushroom (Inonotus obliquus) on cellular NF-$\kappa$B activation and their antioxidant activity. Kor. J. Pharmacogn., 35, 92-97
  29. Takaku, T., Jiang, M., Okuda, H. and Maeda, N. (1997). Isolation of Insulin like substance form Ephedra sinica STAPF. J. Traditional. Med., 14, 358-359
  30. Yamanaka, S., Hashimoto, M., Tobe, M., Kobayashi, K., Sekizawa, J. and Nishimura, M. (1990). A simple method for screening assessment of acute toxicity of chemicals. Arch. Toxicol., 64, 262-268 https://doi.org/10.1007/BF01972985
  31. Yu, H.E., Cho, S.M., Seo, G.S., Lee, B.S., Lee, D.H. and Lee, J.S. (2006). Screening of bioactive compounds from mushroom Pholiota sp. Kor. J. Mycol., 34, 15-21 https://doi.org/10.4489/KJM.2006.34.1.015