DOI QR코드

DOI QR Code

Evaluation of General Toxicity and Genotoxicity of the Silkworm Extract Powder

  • 투고 : 2013.11.27
  • 심사 : 2013.12.17
  • 발행 : 2013.12.31

초록

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent ${\alpha}$-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.

키워드

참고문헌

  1. Bulletin of the World Health Organization. (2004) WHO News. Bull. W. H. O., 82, 635-636.
  2. Hughes, A.B. and Rudge, A.J. (1994) Deoxynojirimycin: synthesis and biological activity. Nat. Prod. Rep., 11, 135-162. https://doi.org/10.1039/np9941100135
  3. Yoshikuni, Y. (1988) Inhibition of intestinal alpha-glucosidase activity and postprandial hyperglycemia by moranoline and its N-alkyl derivatives. Agric. Biol. Chem., 52, 121-128. https://doi.org/10.1271/bbb1961.52.121
  4. Yoshikuni, Y., Ezure, Y., Aoyagi, Y. and Enomoto, H. (1988) Inhibition of intestinal alpha-glucosidase and postprandial hyperglycemia by N-substituted moranoline derivatives. J. Pharmacobiodyn., 11, 356-362. https://doi.org/10.1248/bpb1978.11.356
  5. Junge, B., Matzke, M. and Stltefuss, J. (1996) Chemistry and structure activity relationships of glucosidase inhibitors. Handb. Exp. Pharmacol., 119, 411-482. https://doi.org/10.1007/978-3-662-09127-2_15
  6. Kimura, Y. and Tabata, Y. (2010) Controlled release of stromal cell-derived factor-1 from gelatin hydrogels enhances angiogenesis. J. Biomater. Sci. Poym. Ed., 21, 37-51. https://doi.org/10.1163/156856209X410193
  7. Kong, W.H., Oh, S.H., Ahn, Y.R., Kim, K.W., Kim, J.H. and Seo, S.W. (2008) Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models. J. Agric. Food Chem., 56, 2613-2619. https://doi.org/10.1021/jf073223i
  8. Asai, A., Nakagawa, K., Higuchi, O., Kimura, T., Kojima, Y., Kariya, J, Miyazawa, T. and Oikawa, S. (2011) Effect of mulberry leaf extract with enriched 1-deoxynojirimycin content on postprandial glycemic control in subjects with impaired glucose metabolism. J. Diabetes Invest., 2, 318-323. https://doi.org/10.1111/j.2040-1124.2011.00101.x
  9. Vichasilp, C., Nakangwa, K., Sookwong, P., Higuchi, O., Kimura, F. and Miyazawa, T. (2012) A novel gelatin crossslinking method retards release of mulberry 1-deoxynojirimycin providing a prolonged hypoglycaemic effect. Food chem., 134, 1823-1830. https://doi.org/10.1016/j.foodchem.2012.03.086
  10. Yoshikaki, A. and Hivonu, M. (1976) The structure of moranoline, a piperidine alkaloid form Morus species. Nippon Nogei Kagaku Kaishi, 50, 571-572. https://doi.org/10.1271/nogeikagaku1924.50.11_571
  11. Kimura, T., Nakagawa, K., Kubota, H., Kojima, Y., Goto, Y., Yamaqishi, K., Oita, S., Oikawa, S. and Miyazawa, T. (2007) Food-grade mulberry powder enriched with 1-deoxynojirimycin suppresses the elevation of postprandial blood glucose in humans. J. Agric. Food Chem., 55, 5869-5874. https://doi.org/10.1021/jf062680g
  12. Asano, N., Tomioka, E., Kizu, H. and Matsui, K. (1994) Sugars with nitrogen in the ring isolated from the leaves of Morus bombycis. Carbohydr. Res., 253, 235-245. https://doi.org/10.1016/0008-6215(94)80068-5
  13. Asano, N., Oseki, K., Tomioka, E., Kizu, H. and Matsui, K. (1994) N-containing sugars from Morus alba and their glycosidase inhibitory activities. Carbohydr. Res., 259, 243-255. https://doi.org/10.1016/0008-6215(94)84060-1
  14. Asano, N., Yamashita, T., Yasuda, K., Ikeda, K., Kizu, H., Kameda, Y., Kata, A., Nash, R.J., Lee, H.S. and Ryu, K.S. (2001) Polyhydroxylated alkaloids isolated from mulberrytrees (Morus alba L.) and silkworms (Bombyx mori L.). J Agric. Food Chem., 49, 4208-4213. https://doi.org/10.1021/jf010567e
  15. Kim, J.W., Kim, S.U., Lee, H.S., Kim, I., Ahn, M.Y. and Ryu, K.S. (2003) Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversedphase high-performance liquid chromatography. J. Chromatogr. A, 1002, 93-99. https://doi.org/10.1016/S0021-9673(03)00728-3
  16. Yin, H., Shi, X.Q., Sun, B., Ye, J.J., Duan, Z.A., Zhou, X.L., Cui, W.Z. and Wu, X.F. (2010) Accumulation of 1-deoxynojirimycin in silkworm, Bombyx mori L. J. Zhejiang Univ. Sci. B, 11, 286-291. https://doi.org/10.1631/jzus.B0900344
  17. Akai, H. (1999) New physiological functions of silk material. Shokuhin Kaihatsu, 34, 45-47.
  18. Gotoh, K., Izumi, H., Kanamoto, T., Tamada, Y. and Nakashima, H. (2000) Sulfate fibroin, a novel sulfated peptide derived from silk, inhibits human immunodeficiency virus replication in vitro. Biosci. Biotechnol. Biochem., 64, 1664-1670. https://doi.org/10.1271/bbb.64.1664
  19. Hong, S.E., Park, K.J., Suh, B.S., Do, M.S. and Hyun, C.K. (2002) Effect of silk fibroin hydrolysate on adipocyte metabolism in db/db mice. Korean J. Pharmacogn., 33, 312-318.
  20. Suzuki, N., Fuzimura, A., Nagai, T., Mizumoto, I., Itami, T., Hatate, H., Nozawa, T., Kato, N., Nomoto, T. and Yoda, B. (2004) Antioxidative activity of animal and vegetable dietary fibers. BioFactors, 21, 329-333. https://doi.org/10.1002/biof.552210164
  21. Koyama, H., Utakoji, T. and Ono, T. (1970) A new cell line derived from newborn Chinese hamster lung tissue. Gann, 61, 161-167.
  22. Maron, D.M. and Ames, B.N. (1983) Revised methods for the Salmonella mutagenicity test. Mutat. Res., 113, 173-215. https://doi.org/10.1016/0165-1161(83)90010-9
  23. Green, M.H. and Muriel, W.J. (1976) Mutagen testing using TRP+ reversion in Escherichia coli. Mutat. Res., 38, 3-32. https://doi.org/10.1016/0165-1161(76)90076-5
  24. Japanese Environmental Mutagen Society-Mammalian Mutagenicity Study Group. (1988) Atlas of chromosome aberration by chemicals. JEMS-MMS, Tokyo, Japan.
  25. Schmid, W. (1975) The micronucleus test. Mutat. Res., 31, 9-15. https://doi.org/10.1016/0165-1161(75)90058-8
  26. Han, Z.Z., Xu, H.D., Kim, K.H., Ahn, T.H., Bae, J.S., Lee, J.Y., Gil, K.H., Lee, J.Y., Woo, S.J., Yoo, H.J., Lee, H.K., Kim, K.H., Park, C.K., Zhang, H.S. and Song, S.W. (2010) Reference data of the main physiological parameters in control Spague-Dawley rats from pre-clinical toxicity studies. Lab. Anim. Res., 26, 153-164. https://doi.org/10.5625/lar.2010.26.2.153

피인용 문헌

  1. L. vol.35, pp.6, 2016, https://doi.org/10.1177/1091581816670597
  2. The effect of hemoperfusion on patients with toxic encephalopathy induced by silkworm chrysalis ingestion vol.61, pp.3, 2016, https://doi.org/10.1177/0036933015619291