Korean Journal of Veterinary Research (대한수의학회지)

The Korean Society of Veterinary Science (대한수의학회)
권호 표지

A 90-day repeated-dose oral toxicity study on Flos lonicerae extract in Fischer 344/N rats

금은화(Flos lonicerae) 추출물의 Fischer 344/N 랫드를 이용한 90일간 반복 경구투여 독성시험

  • Accepted : 2008.11.19
  • Published : 2008.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study was performed to evaluate repeated-dose oral toxicities of Flos lonicerae extract in Fischer 344/n rats. Flos lonicerae was administered orally to rats at dose levels of 0, 37, 111, 333, 1,000 and 2,000 mg/kg/day. Each group consisted of 10 rats of each gender. The Flos lonicerae extract was given once a day, 5 times a week, for 90 day repeatedly. This study was conducted in accordance with the Protocol of Korea National Toxicology Program and The Standards of Toxicity Study for Medicinal Products. In the present study, there were no toxicologically significant changes in mortality, clinical signs, body weight gains, ophthalmoscopy, urine analysis, hematology, serum biochemistry, necropsy findings, organ weights, histopathology, estrus cycle and sperm examination of all animals treated with Flos lonicerae extract. These results suggest that the oral no observed adverse-effect level of the test item, Flos lonicerae extract, in rats is higher than 2,000 mg/kg/day in both genders. The target organs were not established.

Keywords

References

  1. 국립독성연구원. KNTP 독성시험 프로토콜. 국립독성연구원, 서울, 2005
  2. 식품의약품안전청. 의약품등의독성시험기준 (고시 제 2005-60 호). 식품의약품안전청, 서울, 2005
  3. 식품의약품안전청. 비임상시험관리기준 (고시 제 2005-79 호). 식품의약품안전청, 서울, 2005
  4. Boorman GA, Eustis SL, Elwell MR, Montgomery CA, Mackenzie WF. Pathology of the Fischer Rat. pp. 127-154. Academic Press, San Diego, 1990
  5. Chai XY, Li SL, Li P. Quality evaluation of Flos lonicerae through a simultaneous determination of seven saponins by HPLC with ELSD. J Chromatogr A 2005, 1070, 43-48 https://doi.org/10.1016/j.chroma.2005.02.031
  6. Chang HM, But PPH. Pharmacology and Applications of Chinese Material Medica. Vol. 2. pp. 787-792, World Scientific Publishing, Singapore, 1986
  7. Chen J, Song Y, Li P. Capillary high-performance liquid chromatography with mass spectrometry for simultaneous determination of major flavonoids, iridoid glucosides and saponins in Flos Lonicerae. J Chromatography A 2007, 1157, 217-226 https://doi.org/10.1016/j.chroma.2007.05.063
  8. Choi CW, Jung HA, Kang SS, Choi JS. Antioxidant constituents and a new triterpenoid glycoside from Flos Lonicerae. Arch Pharm Res 2007, 30, 1-7 https://doi.org/10.1007/BF02977770
  9. Flood MT, Kondo M. Toxicity evaluation of a betagalactosidase preparation produced by Penicillium multicolor. Regul Toxicol Pharmacol 2004, 40, 281-292 https://doi.org/10.1016/j.yrtph.2004.07.011
  10. Greaves P. Histopathology of Preclinical Toxicity Studies. 2nd ed. pp. 254-676. Elsevier, Amsterdam, 2000
  11. Han JS, Park HS. The effects of anti-cancer and immune response of Lonicerae Flos herbalacupuncture. J Kor Acu Mox Soc 2006, 23, 205-218
  12. Han YJ, Lee SD, Choi JH, Jang IS, Park HM. Effects of High Frequency Herbal Medication Administrations on the Liver Functions in Rats. J Kor Oriental Med Soc 2006, 27, 78-90
  13. Jang IS, Yang CS, Han CH. A Review of Herbal Medicinal Products Associated with Toxic Events in Korea. J Kor Oriental Med Soc 2007, 28, 01-10
  14. Kawai H, Kuroyanagi M, Ueno A. Iridoid glucosides from Lonicera japonica Thunb. Chem Pharm Bull (Tokyo) 1988, 36, 3664-66 https://doi.org/10.1248/cpb.36.3664
  15. Kawai H, Kuroyanagi M, Umehara K, Ueno A, Satake M. Studies on the saponins of Lonicera japonica Thunb. Chem Pharm Bull (Tokyo) 1988, 36, 4769-4775 https://doi.org/10.1248/cpb.36.4769
  16. Kim YS, Roh JH, Moon SK, Cho KH, Bae HS, Lee KS. The relations between constant use of herbal medicine and liver injury. J Kyung Hee Univ Med Cent 1999, 15, 71-77
  17. Li HJ, Li P, Ye WC. Determination of five major iridoid glucosides in Flos Lonicerae by highperformance liquid chromatography coupled with evaporative light scattering detection. J Chromatogr A 2003, 1008, 167-172 https://doi.org/10.1016/S0021-9673(03)00978-6
  18. Mei N, Arlt VM, Phillips DH, Heflich RH, Chen T. DNA adduct formation and mutation induction by aristolochic acid in rat kidney and liver. Mutat Res 2006, 602, 83-91 https://doi.org/10.1016/j.mrfmmm.2006.08.004
  19. Ministry of Public Health of the People's Republic of China. Pharmacopoeia of the People's Republic of China. p. 177, Chemical Industry Press, Beijing, 2000
  20. Mohr U, Dungworth DL, Capen CC. Pathobiology of the Aging Rat. pp. 161-172, International Life Sciences Institute, Washington DC, 1992
  21. Park HM, Choi KH, Jung JY, Lee SD. Metal Exposure Through Consumption of Herbal Medicine, and Estimation of Health Risk Among Korean Population. Korean J Environ Health Soc 2006, 32, 186-191
  22. Park SK, Choi BK, Lee EB. Effect of Lonicera Japonica Flower on CCl4-induced Hepatotoxicity. J Appl Pharmacol 2002, 10, 32-36
  23. Pittler MH, Ernst E. Systematic review: hepatotoxic events associated with herbal medicinal products. Aliment Pharmacol Ther 2003, 18, 451-471 https://doi.org/10.1046/j.1365-2036.2003.01689.x
  24. Son KH, Kim JS, Kang SS, Kim HP, Chang HW. Isolation of flavonoids from Lonicera japonica. Kor J Pharmacog 1994, 25, 24-27
  25. Stein U, Greyer H, Hentschel H. Nutmeg (myristicin) poisoning-report on a fatal case and a series of cases recorded by a poison information centre. Forensic Sci Int 2001, 118, 87-90 https://doi.org/10.1016/S0379-0738(00)00369-8
  26. Tae J, Han SW, Yoo JY, Kim JA, Kang OH, Baek OS, Lim JP, Kim DK, Kim YH, Bae KH, Lee YM. Anti-inflammatory effect of Lonicera japonica in proteinase-activated receptor 2-mediated paw edema. Clin Chim Acta 2003, 330, 165-171 https://doi.org/10.1016/S0009-8981(03)00017-2
  27. Tang W, Eisenbrand G. Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine. pp. 621-625, Springer-Verlag, Berlin, 1992
  28. Vanherweghem JL, Depierreux M, Tielemans C, Abramowicz D, Dratwa M, Jadoul M, Richard C, Vandervelde D, Verbeelen D, Vanhaelen-Fastre R, Vanhaelen M. Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese. Lancet 1993, 341, 387-391 https://doi.org/10.1016/0140-6736(93)92984-2
  29. Wirth JH, Hudgins JC, Paice JA. Use of herbal therapies to relieve pain: a review of efficacy and adverse effects. Pain Manag Nurs 2005, 6, 145-167 https://doi.org/10.1016/j.pmn.2005.08.003
  30. Wolf BW, Weisbrode SE. Safety evaluation of an extract from Salacia oblonga. Food Chem Toxicol 2003, 41, 867-874 https://doi.org/10.1016/S0278-6915(03)00038-3
  31. Wu HZ, Luo J, Yin YX, Wei Q. Effects of chlorogenic acid, an active compound activating calcineurin, purified from Flos Lonicerae on macrophage. Acta Pharmacol Sin 2004, 25, 1685-1689
  32. Wu L. Effect of chlorogenic acid on antioxidant activity of Flos Lonicerae extracts. J Zhejiang Univ Sci B 2007, 8, 673-679 https://doi.org/10.1631/jzus.2007.B0673