DOI QR코드

DOI QR Code

Single Dose Oral Toxicity Test of Water Extract of Corni Fructus in ICR Mice

ICR 마우스를 이용한 산수유 건피 추출물의 단회 경구투여 독성시험

  • Hwang-Bo, Hyun (Anti-Aging Research Center, Dong-eui University) ;
  • Kwon, Da Hye (Anti-Aging Research Center, Dong-eui University) ;
  • Kim, Min Young (Anti-Aging Research Center, Dong-eui University) ;
  • Ji, Seon Yeong (Anti-Aging Research Center, Dong-eui University) ;
  • Choi, Eun Ok (Anti-Aging Research Center, Dong-eui University) ;
  • Kim, Sung Ok (Department of Food Science and Biotechnology, College of Engineering, Kyungsung University) ;
  • Jeong, Ji-Suk (Gurye-gun Agricultural Center and Gurye Wildflower Institute) ;
  • Hong, Su Hyun (Anti-Aging Research Center, Dong-eui University) ;
  • Choi, Sung Hyun (Department of System Management, Korea Lift College) ;
  • Park, Cheol (Department of Molecular Biology, College of Natural Sciences and Human Ecology, Dong-eui University) ;
  • Choi, Yung Hyun (Anti-Aging Research Center, Dong-eui University)
  • 황보현 (동의대학교 항노화연구소) ;
  • 권다혜 (동의대학교 항노화연구소) ;
  • 김민영 (동의대학교 항노화연구소) ;
  • 지선영 (동의대학교 항노화연구소) ;
  • 최은옥 (동의대학교 항노화연구소) ;
  • 김성옥 (경성대학교 공과대학 식품응용공학부) ;
  • 정지숙 (구례야생화연구소) ;
  • 홍수현 (동의대학교 항노화연구소) ;
  • 최성현 (한국승강기대학교 승강기시스템관리과) ;
  • 박철 (동의대학교 자연과학대학 분자생물학과) ;
  • 최영현 (동의대학교 항노화연구소)
  • Received : 2018.07.11
  • Accepted : 2019.01.07
  • Published : 2019.01.30

Abstract

Herbal medicines are widely used as therapeutic products in many countries. Corni fructus (CF), the dried ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been used for thousands of years in traditional medicine and has been reported to be effective for the prevention and treatment of various diseases, such as kidney diseases and diabetes. Recent research on CF has documented a wide spectrum of therapeutic properties, which include anti-inflammatory, ant-oxidative, immunomodulatory, and anti-cancer effects. However, there is no information on its safety. Therefore, in this study, the toxicity of water extract of CF to ICR mice was investigated. The mice received a single dose of water extract of CF (1,000, 2,000, and 5,000 mg/kg of body weight) via the oral route. Mortality, clinical signs, body weight changes, gross findings, and weights of the principal organs after 14 d were then assessed. The results revealed no adverse effects of CF as determined by clinical signs, body weights, or organ weights and no gross pathological findings in any of the treatment groups. These results suggest that the 50% lethal dose and approximated lethal dose of CF extract is over 5,000 mg/kg. The findings provide scientific evidence for the safety of CFs.

산수유(Corni Fructus)는 한국을 포함한 아시아 지역에서 오랫동안 전통 의약제로 광범위하게 사용되어 왔다. 최근 연구에 따르면 산수유는 항염증, 항산화, 면역기능 조절 및 항암활성 등과 같은 많은 효능을 가지는 것으로 알려져 있다. 그러나 산수유에 대한 독성 및 안전성에 대해서는 거의 알려져 있지 않은 실정이다. 따라서 본 연구에서는 산수유 열수 추출물(CF)을 대상으로 안전성을 확인하기 위하여 단회 경구 투여에 따른 독성 시험을 실시하였다. 이를 위하여 ICR 마우스를 대상으로 1,000, 2,000 및 5,000 mg/kg의 CF를 경구 투여하였으며, 투여 후 14일 동안의 치사율, 체중 변화, 임상증상, 음수율 및 사료섭취량과 함께 부검 소견, 장기무게 변화, 혈액학 및 혈액생화학적 검사를 실시하였다. 실험 결과에 의하면 CF 투여에 따른 치사율, 임상증상, 체중 및 부검 소견 상의 유의적인 변화는 관찰되지 않았다. 또한 CF 투여에 따른 각 장기의 무게, 혈액학적 및 혈청학적 임상 화학적 지표에도 유의적인 변화는 관찰할 수 없었다. 따라서 CF 단회 경구 투여에 따른 치사량이 5,000 mg/kg 이상일 것으로 추정되어 ICR 마우스에 대하여 급성 독성이 없는 비교적 안전한 물질이라는 것을 알 수 있었으며, 향후 천연 식의약 소재로서의 효능 규명을 통한 활용이 기대된다.

Keywords

Table 1. Experimental design used in this study

SMGHBM_2019_v29n1_112_t0001.png 이미지

Table 2. Body weights change of ICR mice orally treated with CF for 16 days

SMGHBM_2019_v29n1_112_t0002.png 이미지

Table 3. Organ weights of ICR mice orally treated with CF

SMGHBM_2019_v29n1_112_t0003.png 이미지

Table 4. Observed necropsy finding of ICR mice orally treated with CF

SMGHBM_2019_v29n1_112_t0004.png 이미지

Table 5. Levels of hematological analysis in ICR mice orally treated with CF

SMGHBM_2019_v29n1_112_t0005.png 이미지

Table 6. Levels of serum biochemistry analysis in ICR mice orally treated with CF

SMGHBM_2019_v29n1_112_t0006.png 이미지

References

  1. An, Y. A., Hwang, J. Y., Lee, J. S. and Kim, Y. C. 2015. Cornus officinalis methanol extract upregulates melanogenesis in melan-a cells. Toxicol. Res. 31, 165-172. https://doi.org/10.5487/TR.2015.31.2.165
  2. Chan, G. K., Wu, R., Chen, V. P., Zhu, K. Y. and Du, Y. 2018. Quality control on herbal medicine and its application. Evid. Based Complement. Alternat. Med. 2018, 3294398.
  3. Chen, Y., Wu, Y., Gan, X., Liu, K., Lv, X., Shen, H., Dai, G. and Xu, H. 2016. Iridoid glycoside from Cornus officinalis ameliorated diabetes mellitus-induced testicular damage in male rats: Involvement of suppression of the AGEs/RAGE/p38 MAPK signaling pathway. J. Ethnopharmacol. 194, 850-860. https://doi.org/10.1016/j.jep.2016.10.079
  4. Coates, A., Abraham, S., Kaye, S. B., Sowerbutts, T., Frewin, C., Fox, R. M. and Tattersall, M. H. 1983. On the receiving end-patient perception of the side-effects of cancer chemotherapy. Eur. J. Cancer Clin. Oncol. 19, 203-208. https://doi.org/10.1016/0277-5379(83)90418-2
  5. Park, C. H., Noh, J. S., Kim, J. H., Tanaka, T., Zhao, Q., Matsumoto, K., Shibahara, N. and Yokozawa, T. 2011. Evaluation of morroniside, iridoid glycoside from Corni Fructus, on diabetes-induced alterations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice. Biol. Pharm. Bull. 34, 1559-1565. https://doi.org/10.1248/bpb.34.1559
  6. Food and Drug Safety. 2000. Research for establishing rational management system of functional foods.
  7. Jang, I., Yang, C., Lee, S. and Han, C. 2007. A review of herbal medicinal products associated with toxic events in Korea. J. Kor. Oriental Med. 28, 1-10.
  8. Jeng, H., Wu, C. M., Su, S. and Chang, W. C. 1997. A substance isolated from Cornus officinalis enhances the motility of human sperm. Am. J. Chin. Med. 25, 301-306. https://doi.org/10.1142/S0192415X97000330
  9. Kennedy, B. K., Berger, S. L., Brunet, A., Campisi, J., Cuervo, A. M., Epel, E. S., Franceschi, C., Lithgow, G. J., Morimoto, R. I., Pessin, J. E., Rando, T. A., Richardson, A., Schadt, E. E., Wyss-Coray, T. and Sierra, F. 2014. Geroscience: linking aging to chronic disease. Cell 159, 709-713. https://doi.org/10.1016/j.cell.2014.10.039
  10. Kim, H. and Song, M. 2011. Analysis and recordings of orally transmitted knowledge about medicinal plants in the southern mountainous region of Korea. J. Ethnopharmacol. 134, 676-696. https://doi.org/10.1016/j.jep.2011.01.024
  11. Kim, H. U., Ryu, J. Y., Lee, J. O. and Lee, S. Y. 2015. A systems approach to traditional oriental medicine. Nat. Biotechnol. 33, 264. https://doi.org/10.1038/nbt.3167
  12. Kim, S., Kim, B. and Lee, Y. 2012. Effects of Corni fructus on ovalbumin-induced airway inflammation and airway hyper-responsiveness in a mouse model of allergic asthma. J. inflamm (Lond). 9, 9. https://doi.org/10.1186/1476-9255-9-9
  13. Korea Food & Drug Administration. 2015. Toxicity test standards for medicines. Korea Food and Drug Administration Notice (2015-82).
  14. Korea Health Industry Development Institute. 2006. The tendency of research and development of internal and external natural source remedies. The second: Plan for Promotion of Natural Medicine Research & Development. 1-20.
  15. Kwon, C., Lee, B., Suh, H., Chung, S. and Kim, J. W. 2018. Efficacy and safety of auricular acupuncture for cognitive impairment and dementia: A systematic review. Evid. Based Complement Alternat. Med. 2018, 3426078.
  16. Lee, S. J., Kim, E. H. and Lee, H. G. 2008. Development of rice wines using Cornus officinalis and Sutellaria baicalensis by antioxidant activity tests. Kor. J. Food Sci. Technol. 40, 21-30.
  17. Lee, S., Kim, S. Y., Han, S., Kim, H., Ham, S. and Kang, I. 2006. Corni fructus scavenges hydroxy radicals and decreases oxidative stress in endothelial cells. J. Med. Food 9, 594-598. https://doi.org/10.1089/jmf.2006.9.594
  18. Mau, J., Chen, C. and Hsieh, P. 2001. Antimicrobial effect of extracts from Chinese chive, cinnamon, and corni fructus. J. Agr. Food Chem. 49, 183-188. https://doi.org/10.1021/jf000263c
  19. McGeer, P. L. and Mcgeer, E. G. 2004. Inflammation and the degenerative diseases of aging. Ann. N. Y. Acad. Sci. 1035, 104-116. https://doi.org/10.1196/annals.1332.007
  20. Miller, G. E., Chen, E. and Parker, K. J. 2011. Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms. Psychol. Bull. 137, 959. https://doi.org/10.1037/a0024768
  21. Misra, R. 1998. Modern drug development from traditional medicinal plants using radioligand receptor-binding assays. Med. Res. Rev. 18, 383-402. https://doi.org/10.1002/(SICI)1098-1128(199811)18:6<383::AID-MED3>3.0.CO;2-A
  22. Molkara, T., Akhlaghi, F., Ramezani, M. A., Salalri, R., Vakili, V., Kamalinejad, M., Bordbar, M. R. F., Ghorbani, A. and Motavasselian, M. 2018. Effects of a food product (based on Daucus carota) and education based on traditional Persian medicine on female sexual dysfunction: a randomized clinical trial. Electron. Physician 10, 6577-6587. https://doi.org/10.19082/6577
  23. Newman, D. J., Cragg, G. M. and Snader, K. M. 2000. The influence of natural products upon drug discovery. Nat. Prod. Rep. 17, 215-234. https://doi.org/10.1039/a902202c
  24. Park, C. H., Xu, F. H., Roh, S., Song, Y. O., Uebaba, K., Noh, J. S. and Yokozawa, T. 2015. Astaxanthin and Corni Fructus protect against diabetes-induced oxidative stress, inflammation, and advanced glycation end product in livers of streptozotocin- induced diabetic rats. J. Med. Food 18, 337-344. https://doi.org/10.1089/jmf.2014.3174
  25. Peng, Q., Wei, Z. and Lau, B. H. 1998. Fructus corni attenuates oxidative stress in macrophages and endothelial cells. Am. J. Chin. Med. 26, 291-300. https://doi.org/10.1142/S0192415X98000336
  26. Tao, J., Zhao, M., Joang, S., Pu, X. and Wei, X. 2018. Comparative metabolism of two major compounds in Fructus Corni extracts by gut microflora from normal and chronic nephropathy rats in vitro by UPLC-Q-TOF/MS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 1073, 170-176. https://doi.org/10.1016/j.jchromb.2017.12.025
  27. Tokuyasu, N., Shomori, K., Amano, K., Honjo, S., Sakamoto, T., Watanabe, J., Amisaki, M., Morimoto, M., Uchinaka, E., Yagyu, T., Saito, H., Ito, H. and Fujiwara, Y. 2018. Indirubin, a constituent of the Chinese herbal medicine Qing-Dai, attenuates dextran sulfate sodium-induced murine colitis. Yonago Acta. Med. 61, 128-136. https://doi.org/10.33160/yam.2018.06.005