Single Oral Dose Toxicity Test of Choweseuncheng-tang, a Polyherbal Formula in ICR Mice

조위승청탕의 마우스 경구 단회 투여독성 평가

  • Jung, Tae Young (3rd Department of Internal Medicine, College of Korean Medicine, Daegu Haany University)
  • 정태영 (대구한의대학교 한의과대학 진단학교실)
  • Received : 2013.11.20
  • Accepted : 2013.12.29
  • Published : 2014.02.25

Abstract

The object of this study was to evaluate the single dose toxicity of Choweseuncheng-tang (CWS), a polyherbal formula have been traditionally used as prevention or treatment agent for various diseases as Tae-eumin prescription on Korean medicinal theory, Sasang-euihak, in male and female mice. Aqueous extracts of CWS (yield = 11.00%) was administered to female and male mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principle organs were also examined. As results, we could not find any CWS treatment related mortality and clinical signs, changes in the body and organ weights, gross findings and changes in histopathology of principle organs, except for some dose-independent accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of CWS aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines, and can be safety used in clinics.

Keywords

References

  1. 홍순용, 이을호. 사상의학원론. 서울, 행림출판사, pp 344, 350-357, 1977.
  2. 이제마. 동의수세보원. 서울, 행림출판사, p 116, 122, 1979.
  3. 박인상. 동의사상요결. 서울, 소나무, p 156, 1991.
  4. 유지걸, 김남재, 김종우, 이경섭, 홍남두. 生藥 複合製劑의 藥效 硏究 第26報 - 調胃升淸湯의 抗痙攣, 鎭痛, 鎭靜, 摘出腸管, 血管, 血壓및 呼吸에 對한 影響. 생약학회지 17(1):12-18, 1986.
  5. 우주영, 김종우, 황의완, 김현택, 박순권. 調胃升淸湯이 흰쥐의 방사형 미로 학습과 기억에 미치는 影響. 동의신경정신과학회지 8(1):69-79, 1997.
  6. 김형순, 김경요, 고기덕, 김일환, 송승연. 調胃升淸湯 煎湯液이 XO/HX에 의해 損傷된 培養 海馬神經細胞에 미치는 效果. 사상체질의학회지 14(1):67-78, 2002.
  7. 김보균, 김종우, 김현택, 정경천, 황의완. 알츠하이머형 치매환자에 대한 調胃升淸湯의 효능 -청각 ERP 및 K-DRS의 성적 변화를 통하여-. 동의신경정신과학회지 14(2):43-59, 2003.
  8. 조성훈, 김종우, 김현택, 정경천, 황의완. 調胃升淸湯이 초기 Dementia of Alzheimer type 환자의 인지기능 변화에 미치는 효과. 동의신경정신과학회지 14(1):17-26, 2003.
  9. 함통일, 이수경, 고병희, 최경주. 浮腫이 발생한 太陰人 中風患者의 調胃升淸湯 合 건율제조탕 치험 1례. 대한한방성인병학회지 10(1):39-45, 2005.
  10. 김경욱, 김종우, 김현택, 지상은, 김운령, 황의완. 憂鬱症모델 흰쥐에 대한 調胃升淸湯과 St. John's Wort의 抗憂鬱效果에 관한 비교 연구. 동의신경정신과학회지 15(1):43-64, 2004.
  11. 류재면, 김종우, 지상은, 김은주, 박은혜, 황의완. 憂鬱症모델 흰쥐에 대한 調胃升淸湯과 fluoxetine의 抗憂鬱效果 비교. 동의신경정신과학회지 15(1):27-41, 2004.
  12. 이재은, 김병우, 임태진, 김동희, 권기록. 調胃升淸湯의 알코올 및 熱水추출물이 지방세포 대사에 미치는 영향. 대한약침학회지 11(1):127-141, 2008.
  13. 이미정, 양가은, 이지숙, 노현인, 윤다래, 안수민, 류재환. 調胃升淸湯의 고지방식이 유도 비만 쥐에서 비만 및 고지혈증에 대한 효과 연구. 대한한의학회지 32(4):37-47, 2011.
  14. 박성식, 한진수. 調胃升淸湯의 胃粘膜 損傷 防禦效果에 관한 硏究. 사상체질의학회지 14(1):100-111, 2002.
  15. 한국식품의약품안전청. 의약품 등의 독성시험기준. 한국식품의약품안전청 고시 제 2009-116호. 2009.
  16. Irwin, S. Comprehensive observational assessment: Ia. A systemic, quantitative procedure for assessing the behavioral and physiological state of the mouse. Psychopharmacology. 13(3):222-257, 1968. https://doi.org/10.1007/BF00401402
  17. Dourish, C.T. Effects of drugs on spontaneous motor activity. In Experimental Psychopharmacology (Greenshaw AJ and Dourish CT, Ed.), Humana Press, Clifton, pp 325-334, 1987.
  18. Levene, A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clin Otalary 6(3):145-151, 1981. https://doi.org/10.1111/j.1365-2273.1981.tb01800.x
  19. Ludbrook, J. Update: microcomputer statistics packages. A personal view. Clin Exp Pharmacol Physiol. 24(3-4):294-296,1997. https://doi.org/10.1111/j.1440-1681.1997.tb01823.x
  20. Lee, H.S., Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Jung, Y.M., Ku, S.K. Single oral dose toxicity studies of Polycan, a ${\beta}$-glucan originated from Aureobasidium in mice. Toxicol Res. 21(4):361-365, 2005.
  21. Lee, J.H., Yang, K.J., Shin, H.D., Park, B.R., Son, C.W., Jang, H.J., Park, D.C., Lee, H.S., Ku, S.K. Single Subcutaneous Dose Toxicity of Polycan(R), a ${\beta}$-Glucan Originated from Aureobasidium in Mice. Lab Anim Res. 21(4):299-305, 2005.
  22. Roh, S.S., Ku, S.K. Mouse single oral dose toxicity study of DHU001, a polyherbal formula. Toxicol Res. 26(1):53-59, 2010. https://doi.org/10.5487/TR.2010.26.1.053
  23. Lee, W.H., Gam, C.O., Ku, S.K., Choi, S.H. Single oral dose toxicity test of platycodin D, a saponin from platycodin radix in mice. Toxicol Res. 27(4):217-224, 2011. https://doi.org/10.5487/TR.2011.27.4.217
  24. Plata, E.J., Murphy, W.H. Growth and hematologic properties of the BALB/wm strain of inbred mice. Lab Anim Sci. 22(5):712-720, 1972.
  25. Yamaguchi, C., Fujita, S., Obara, T., Ueda, T. Effects of room temperature on reproduction, body weight and organ weights, food and water intakes, and hematology in mice. Exp Anim. 32(1):1-11, 1983.
  26. Banks, W.J. Female reproductive system in Applied veterinary histology. (Banks, W.J., Ed.), Williams & Wilkins, Baltimore, pp 506-526, 1986.
  27. Pineda, M.H. Female reproductive system in Veterinary endocrinology and reproduction (McDonald, LE, Pineda MH, Eds), Lea & Febiger, Philadelphia, pp 303-354, 1989.
  28. US Environmental Protection Agency. Health Effects Test Guidelines OPPTS 870.100, Acute Toxicity Testing Background. US EPA August, Washington, USA, 1998.