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Single- and Repeated-Dose Oral Toxicity in Rats and Bacterial Reverse Mutation Test of Morus alba L. Extracts

상지추출물의 단회/반복투여 독성 및 복귀돌연변이능 평가

  • Han, Taewon (Division of Functional Food Research, Korea Food Research Institute) ;
  • Um, Min Young (Division of Functional Food Research, Korea Food Research Institute) ;
  • Lim, Young Hee (School of Biosystem and Biomedical Science, College of Health Science, Korea University) ;
  • Kim, Jeong-Keun (Department of Chemical Engineering and Biotechnology, Korea Polytechnic University) ;
  • Kim, In-Ho (Division of Functional Food Research, Korea Food Research Institute)
  • 한태원 (한국식품연구원 기능성식품 연구본부) ;
  • 엄민영 (한국식품연구원 기능성식품 연구본부) ;
  • 임영희 (고려대학교 보건과학대학 바이오시스템의과학부) ;
  • 김정근 (한국산업기술대학교 생명화학공학과) ;
  • 김인호 (한국식품연구원 기능성식품 연구본부)
  • Received : 2016.06.14
  • Accepted : 2016.08.17
  • Published : 2016.10.31

Abstract

This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.

상지추출물의 독성을 복귀돌연변이, 단회투여 및 반복투여 독성 등 다각적으로 적용하여 평가하였다. 상지추출물의 복귀돌연변이 실험을 Salmonella Typhimurium의 히스티딘 요구성 균주 4종과 Escherichia coli의 트립토판 요구성 균주 1종을 이용하여 대사활성계 적용 및 비적용 하에서 Ames test를 실시하였다. 대사활성계 유무에 상관없이 $5,000{\mu}g/plate$의 처리 농도까지 복귀돌연변이 콜로니 수는 증가되지 않았으므로 상지추출물은 복귀돌연변이를 유발하지 않는 것으로 판단하였다. SD rats 암수에 1,250, 2,500 및 5,000 mg/kg의 농도로 단회 경구투여 하고 14일 동안 일반증상, 운동성, 식이섭취량, 사망 여부 및 체중 변화를 조사한 결과, 사망동물은 관찰되지 않았으며 대조군과 비교하여 실험동물의 암수 모두에서 시험물질 투여에 따른 일반적인 증상변화는 나타나지 않았다. 대조군과 시험군은 모두 정상적인 체중 증가가 관찰되었고 대조군과 비교하여 상지추출물 투여군의 유의적인 체중 변화는 나타나지 않았으며, $LD_{50}$은 암수 모두 5,000 mg/kg 이상인 것으로 판단하였다. 또한, 상지추출물을 500, 1,000 및 2,000 mg/kg/d의 용량으로 28일간 반복 경구투여 하면서 실험동물의 일반증상, 사망동물의 유무, 체중 변화, 식이섭취량, 혈액학적 및 혈액생화학적 변화, 부검 후 육안적 검사를 통한 병변의 유무를 관찰하였다. 시험기간 동안 암수 모든 군에서 반복 투여로 인한 사망동물이 없었으며 정상적인 체중 증가가 나타났다. 대조군과 비교하여 상지추출물의 투여에 따른 체중 변화는 통계학적으로 유의성이 없었으며 암수 모두 대조군과 비교하여 식이섭취량의 차이 및 유의할만한 일반증상도 관찰되지 않았다. 시험물질의 투여에 따른 장기 무게, 혈액학적 분석 결과 및 혈액생화학적 분석 결과 등에서도 독성 및 이상소견이 발견되지 않았다.

Keywords

References

  1. The Korea Food and Drug Administration. 2013. National standard of traditional medicinal (herbal and botanical) materials. Shinilbooks, Seoul, Korea. p 197.
  2. Shi YW, Wang CP, Wang X, Zhang YL, Liu L, Wang RW, Ye JF, Hu LS, Kong LD. 2012. Uricosuric and nephroprotective properties of Ramulus mori ethanol extract in hyperuricemic mice. J Ethnopharmacol 143: 896-904. https://doi.org/10.1016/j.jep.2012.08.023
  3. Lim YH, Kim KH, Kim JK. 2015. Source, biosynthesis, biological activities and pharmacokinetics of oxyresveratrol. Korean J Food Sci Technol 47: 545-555. https://doi.org/10.9721/KJFST.2015.47.5.545
  4. Kim BS. 2008. Antihypertensive effect of active compounds from stem of Morus alba. PhD Dissertation. Konyang University, Daejeon, Korea.
  5. Ham I, Jeong E, Lee B, Chio H. 2008. The study on anti-hypertensive and anti-diabetic effect of Mori ramulus. Kor J Herbology 23: 203-212.
  6. Kim HS, Jeong JC. 2002. Effects of Ramulus mori extract on obesity and lipid metabolism in high fat diet rats. J Korean Oriental Med 23: 64-72.
  7. Cha YY. 2007. Comparative study on antioxidative effects of Mori ramulus and Mori cortex. Korean J Oriental Physiology & Pathology 21: 934-939.
  8. Park HM, Hong JH. 2014. Effect of extraction methods on antioxidant activities of Mori ramulus. J Korean Soc Food Sci Nutr 43: 1709-1715. https://doi.org/10.3746/jkfn.2014.43.11.1709
  9. Shin JY. 2001. Screening of natural products that have activities against skin-aging. Korean J Food Nutr 14: 568-572.
  10. Park SY, Kim JS, Lee BH, Lim SC, Lee SN, Leem KH, Lee KM. 2009. Whitening effects of Mori Ramulus, Mori Cortex Radicis and Mori Folium herbal-acupuncture solution after fermentation and heating. J Korean Acupuncture & Moxibustion Society 26: 91-98.
  11. Jeong HL, Kim HW, Kim JH, Kim JH, Kim D. 2012. Cosmetic effect of mixed plant extracts including Saururus chinensis, Morus bombycis stem and Morus papyrifera stem. Korean Chem Eng Res 50: 610-613. https://doi.org/10.9713/kcer.2012.50.4.610
  12. Ames BN, Mccann J, Yamasaki E. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian- microsome mutagenicity test. Mutat Res 31: 347-364. https://doi.org/10.1016/0165-1161(75)90046-1
  13. Maron DM, Ames BN. 1983. Revised methods for the Salmonella mutagenicity test. Mutat Res 113: 173-215. https://doi.org/10.1016/0165-1161(83)90010-9
  14. Zimmerman HJ. 1982. Chemical hepatic injury and its detection. In Toxicology of the Liver. Plaa G, Hewitt WR, eds. Raven Press, New York, NY, USA. p 1-45.
  15. Petterino C, Argentino-Storino A. 2006. Clinical chemistry and haematology historical data in control Sprague-Dawley rats from pre-clinical toxicity studies. Exp Toxicol Pathol 57: 213-219. https://doi.org/10.1016/j.etp.2005.10.002
  16. Hwang SY, Kwon W, Chai HY, Cho YM, Lee NJ, Ryu JM, Sin JS, Kim TM, Cho JH, Kim EJ, Park JH, Kang JK, Kim YB. 2004. Four-week repeated-dose toxicity study on Mori radicis cortex. Korean J Lab Anim Sci 20: 283-290.

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