The Anticancer Effect of Inonotus obliquus Pilat (Chaga) Processed by Nanomill Technology In vivo

나노밀 가공된 차가버섯의 항암효과

  • Kim, Dong-Heui (Department of Environmental Medical Biology, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Teng, Yung-Chien (Department of Environmental Medical Biology, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Yoon, Yang-Sook (Department of Environmental Medical Biology, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Qi, Xu-Feng (Department of Environmental Medical Biology, Institute of Basic Medical Science, Wonju College of Medicine, Yonsei University) ;
  • Jeong, Hyun-Seok (Leejema Ltd., Hongcheon Life Health Research Center) ;
  • Chang, Byung-Soo (Department of Cosmetology, Hanseo University) ;
  • Lee, Kyu-Jae (Department of Environmental Medical Biology, Institute of Lifelong Health, Wonju College of Medicine, Yonsei University)
  • 김동희 (연세대학교 원주의과대학 환경의생물학교실, 기초의학연구소) ;
  • 등영건 (연세대학교 원주의과대학 환경의생물학교실, 기초의학연구소) ;
  • 윤양숙 (연세대학교 원주의과대학 환경의생물학교실, 기초의학연구소) ;
  • 최주봉 (연세대학교 원주의과대학 환경의생물학교실, 기초의학연구소) ;
  • 정현석 (주식회사 이제마) ;
  • 장병수 (한서대학교 보건학부 피부미용학과) ;
  • 이규재 (연세대학교 원주의과대학 환경의생물학교실, 평생건강사업단)
  • Received : 2009.04.16
  • Accepted : 2009.06.20
  • Published : 2009.06.30

Abstract

Extracts and fractions of Inonotus obliquus (Chaga in Russia) have been known to have various biological activities, including antimutagenic, anticancer, antioxidative, and immunostimulating effects. This study was performed to confirm anticancer effect of 10% superfine Chaga mushroom processed by nano-mill technology on C57BL/6 mice. Chaga particles belonged in the size of 1 ${\mu}m$ was about 40% after nanomill processing according to the volume distribution. As the result of subcutaneous injection of B16BL6 melanoma cells to the mice, the tumor volume (p<0.001) and tumor weight (p<0.01) was significantly decreased in the experimental (NCh) group as compared with control (C) group and the tumor growth inhibitory rate was 29.2%. On examination of survival rate after intraperitoneal injection of B16BL6 melanoma cells, the mean survival time per a mouse was 17.7 and 26.0 days in C and NCh group respectively. The survival rate of NCh group was 40% when that of C group was 0% at the 35th day. On the result of examination to confirm histological toxicity by Chaga superfine particles, both groups did not show any morphological and pathological changes in the small and large intestine under the light microscope. These results suggest that feeding of superfine Chaga produced by nanomill technique has a tumor growth inhibitory effect in vivo.

차가버섯(Inonotus obliquus)의 추출물과 분획들은 항돌연변이, 항암, 항산화 및 면역자극 효과 등을 비롯하여 다양한 생물학적 활성을 갖는 것으로 알려져 있다. 본 연구는 나노분쇄 기법으로 제작된 10% 차가사료를 C57BL/6 생쥐에게 식이한 후 항암효과를 확인하기 위해 시행되었다. 부피평균에 의한 입도분석에 따르면 1 ${\mu}m$ 내에 포함되는 초미세 차가버섯 입자는 전체의 40%인 것으로 나타났다. 생쥐에게 B16BL6 흑색종세포를 피하로 주사한 결과, 종양의 부피(p<0.001)와 무게(p<0.01)는 초미세 차가버섯을 식이한 실험군(Nch)이 일반사료를 먹인 대조군(C)에 비해 현저히 감소하였고, 종양성장 억제율은 29.2%를 나타내었다. 흑색종 세포를 복강 내로 주사한 후 생존율을 관찰한 결과, 마리 당 평균 생존기간은 대조군과 실험군이 각각 17.7일과 26.0일이었다. 대조군이 모두 사망한 날인 35일 째 실험군의 생존율은 40%를 보여주었다. 초미세 차가입자가 소화기관에 문제를 유발시킬 수 있는 가능성 때문에 안전성을 확인하기 위해 소장과 대장을 조직학적으로 관찰한 결과 두 군 모두 형태학적 또는 병리학적 변화는 관찰되지 않았다.

Keywords

References

  1. Babitskaia VG, Shcherba VV, Ikonnikova NV: Melanin complex of the fungus Inonotus obliquus. Prikl Biokhim Mikrobiol 36(4) : 439-444, 2000
  2. Cui Y, Kim DS, Park KC: Antioxidant effect of Inonotus obliquus. J Ethnopharmacol 96 : 79-85, 2005 https://doi.org/10.1016/j.jep.2004.08.037
  3. Federico A, Morgillo F, Tuccillo C, Ciardiello F: Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 121(11) : 2381-2386, 2007 https://doi.org/10.1002/ijc.23192
  4. Florence AT, Hillery AM, Hussain N, Jani PU: Factors affecting the oral uptake and translocation of polystyrene nanoparticles: histological and analytical evidence. J Drug Target 3(1) : 65-70, 1995 https://doi.org/10.3109/10611869509015936
  5. Jarosz A, Skorska M, Rzymowska J, Kochmanska-Rdest J, Malarczyk E: Effect of the extracts from fungus Inonotus obliquus on catalase level in HeLa and nocardia cells. Acta Biochim Pol 37(1) : 149-151, 1990
  6. Kim HG, Yoon DH, Kim CH, Shrestha B, Chang WC, Lim SY, Lee WH, Han SG, Lee JO, Lim MH, Kim GY, Choi S, Song WO, Sung JM, Hwang KC, Kim TW: Ethanol extracts of Inonotus obliquus inhibits lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells. J Med food 10(1) : 80-89, 2007 https://doi.org/10.1089/jmf.2006.156
  7. Kim YO, Han SB, Lee HW, Ahn HJ, Yoon YD, Jung JK, Kim HM, Shin CS: Immuno-stimulating effect of the endo-polysaccharide produced by submerged culture of Inonotus obliquus. Life Sci 77 : 2438-2456, 2005 https://doi.org/10.1016/j.lfs.2005.02.023
  8. Kim YO, Park HW, Kim JH, Lee JY, Moon SH, Shin CS: Anticancer effect and structural characterization of endo-polysaccharide from cultivated mycelia of Inonotus obliquus. Life Sci 79 : 72-80, 2006 https://doi.org/10.1016/j.lfs.2005.12.047
  9. Lee IK, Kim YS, Jang YW, Jung JY, Yun BS: New antioxidant polyphenols from the medicinal mushroom Inonotus obliquus. Bioor Med Chem Letters 17 : 6678-6681, 2007 https://doi.org/10.1016/j.bmcl.2007.10.072
  10. Nakajima Y, Sato Y, Konishi T: antioxidant small phenolic ingredients in Inonotus obliquus (persoon) Pilat (Chaga). Chem Pharm Bull 55(8) : 1222-1226, 2007 https://doi.org/10.1248/cpb.55.1222
  11. Nakata T, Yamada T, Taji S, Ohishi H, Wada S, Tokuda H, Sakuma K, Tanaka R: Structure determination of inonotsuoxides A and B and in vivo anti-tumor promoting activity of inotodiol from the sclerotia of Inonotus obliquus. Bioor Med Chem 15 : 257-264, 2007 https://doi.org/10.1016/j.bmc.2006.09.064
  12. Park JR, Park JS, Jo EH, Hwang JW, Kim SJ, Ra JC, Aruoma OI, Lee YS, Kang KS: Reversal of the TPA-induced inhibition of gap junctional intercellular communication by Chaga mushroom (Inonotus obliquus) extracts: effects on MAP kinases. Biofactors 27(1-4) : 147-155, 2006 https://doi.org/10.1002/biof.5520270113
  13. Park YM, Won JH, Kim YH, Choi JW, Park HJ, Lee KT: In vivo and in vitro anti-inflammatory and anti-nociceptive effects of the methanol extract of Inonotus obliquus. J Ethnopharmacol 101(1-3) : 120-128, 2005 https://doi.org/10.1016/j.jep.2005.04.003
  14. Plotnikov A, Fishman D, Tichler T, Korenstein R, Keisari Y: Low electric field enhanced chemotherapy can cure mice with CT-26 colon carcinoma and induced anti-tumour immunity. Clin Exp Immunol 138 : 410-416, 2004 https://doi.org/10.1111/j.1365-2249.2004.02636.x
  15. Reid DA: Inonotus obliquus (pers. Ex Fr.) pilat in Britain. Trans Br Mycol Soc 67(2) : 329-332, 1976 https://doi.org/10.1016/S0007-1536(76)80140-4
  16. Saar M: Fungi in Khanty fork medicine. J Ethnopharmacol 31(2) : 175-179, 1991 https://doi.org/10.1016/0378-8741(91)90003-V
  17. Shashkina MY, Shashkin PN, Sergeev AV: Chemical and medicobiological properties of chaga (review). Pharm Chem J 40(10) : 560-568, 2006 https://doi.org/10.1007/s11094-006-0194-4
  18. Sung B, Pandey MK, Nakajima Y, Nishida H, Konishi T, Chatur-vedi MM, Aggarwal BB: Identification of a novel blocker of I$\kappa$B$\alpha$ kinase activation that enhances apoptosis and inhibits proliferation and invasion by suppressing nuclear factor-$\kappa$B. Mol Cancer Ther 7(1) : 191-201, 2008 https://doi.org/10.1158/1535-7163.MCT-07-0406
  19. Valko M, Rhodes CJ, Moncol J, Izakovic M, Mazur M: Free radicals, metals and antioxidants in oxidative stress induced cancer. Chem Biol Interact 160(1) : 1-40, 2006 https://doi.org/10.1016/j.cbi.2005.12.009
  20. Volkheimer G: Passage of particles through the wall of the gastrointestinal tract. Environ Health Persp 9 : 215-225, 1974 https://doi.org/10.2307/3428287
  21. Wasser SP: Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl Microbiol Biotechnol 60 : 258-274, 2002 https://doi.org/10.1007/s00253-002-1076-7
  22. Youn MJ, Kim JK, Park SY, Kim Y, Kim SJ, Lee JS, Chai KY, Kim HJ, Chi MX, So HS, Kim KY, Park R: Chaga mushroom (Inonotus obliquus) induced G0/G1 arrest and apoptosis in human hepatoma HepG2 Cells. World J Gastroenterol 14(4) : 511-517, 2008 https://doi.org/10.3748/wjg.14.511
  23. Zjawiony JK: Biologically active compounds from Aphyllophorales (polypore) fungi. J Nat Prod 67 : 300-310, 2004 https://doi.org/10.1021/np030372w