DOI QR코드

DOI QR Code

Single-dose Intramuscular Toxicity Studies of Shinbaro3 Pharmacopunture in Sprague-Dawley Rats and Beagle Dogs

SD (Sprague-Dawley) 랫드와 비글견을 이용한 신바로3 약침의 단회 근육투여 독성실험

  • Lee, Jin-Ho (Jaseng Spine and Joint Research Institute Jaseng Medical Foundation) ;
  • Lee, In-Hee (Jaseng Spine and Joint Research Institute Jaseng Medical Foundation) ;
  • Lee, Jae-Woong (Jaseng Spine and Joint Research Institute Jaseng Medical Foundation) ;
  • Kim, Eun-Jee (Jaseng Spine and Joint Research Institute Jaseng Medical Foundation) ;
  • Kim, Min-Jeong (Jaseng Spine and Joint Research Institute Jaseng Medical Foundation)
  • 이진호 (자생의료재단 척추관절연구소) ;
  • 이인희 (자생의료재단 척추관절연구소) ;
  • 이재웅 (자생의료재단 척추관절연구소) ;
  • 김은지 (자생의료재단 척추관절연구소) ;
  • 김민정 (자생의료재단 척추관절연구소)
  • Received : 2015.03.16
  • Accepted : 2015.03.31
  • Published : 2015.04.30

Abstract

Objectives To assess the safety of Shinbaro3 Pharmacopuncture by analyzing the potential single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture at various dose levels in SD (Spraque-Dawley) rats and Beagle dogs. Methods For evaluation of single-dose intramuscular toxicity of Shinbaro3 Pharmacopuncture, 40 SD rats (20 male and 20 famale) and 4 Beagle dogs (2 male and 2 female) were used. The rats were divided in four groups of 10 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.3, 0.6 and 1.2 mg/kg in distilled water, and distilled water as a vehicle control group, respectively. The Beagle dogs were divided into two groups of 2 each, and treated intramuscularly with Shinbaro3 Pharmacopuncture at doses of 0.15, and 0.3 mg/kg in distilled water, respectively, and signs of toxicity were observed. After a wash-out period of 3 days, the procedure was repeated with Shinbaro3 Pharmacopuncture at doses of 0.6, and 1.2 mg/kg in distilled water, respectively. Mortality, body weight changes, and necropsy findings were examined during the study period. Results There were no mortalities in either the SD rats or Beagle dogs. There were also no significant differences in adverse effects, body weight, or necropsy findings between the Shinbaro3 Pharmacopuncture and control groups. Conclusions There results suggest that the lethal dose 50 ($LD_{50}$) and approximate lethal dose (ALD) value of the test substance Shinbaro3 Pharmacopuncture are higher than 1.2 mg/kg in SD rats and Beagle dogs.

References

  1. Grant L, Mcbean DE, Fyfe L, Warnock AM. A review of the biological and potential therapeutic actions of Harpagophytum procumbens. Phytotherapy Research. 2007; 21(3):199-209. https://doi.org/10.1002/ptr.2029
  2. Baghdikian B, Lanhers MC, Fleurentin J, Ollivier E, Maillard C, Balansard G, Mortier F. An analytical study, anti-inflammatory and analgesic effects of Harpagophytum procumbens and Harpagophytu mzeyheri. Planta-Medica. 1997;63:171-6. https://doi.org/10.1055/s-2006-957638
  3. Haag-Berrurier M, Kuballa B, Anton R. Dosage des glucoiridoides totaux dans la racine d' Harpagophytum procumbens DC und Harpagophytum zeheri DECNE. Planta-Medica. 1978;12:197-206.
  4. Burger JFW, Brandt EV, Ferreira D. Iridoid and phenolic glycosides from Harpagophytum procumbens. Phytochemistry. 1987;26(5):1453-7. https://doi.org/10.1016/S0031-9422(00)81833-6
  5. Kaszkin M, Beck KF, Koch E, Erdelmeier C, Kusch S, Pfeilschifter J, Loew D. Downregulation of iNOS expression in rat mesangial cells by special extracts of Harpagophytum procumbens derives from harpagoside- dependent and independent effects. Phytomedicine. 2004; 11(7):585-595. https://doi.org/10.1016/j.phymed.2004.02.003
  6. Gunther M, Laufer S, Schmidt PC. High anti-inflammatory activity of harpagoside-enriched extracts obtained from solvent-modified super- and subcritical carbon dioxide extractions of the roots of harpagophytum procumbens. Phytochemical analysis. 2006;17(1):1-7. https://doi.org/10.1002/pca.822
  7. Chrubasik S, Sporer F, Dillmann-Marschner R, Friedmann A, Wink M. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets. Phytomedicine. 2000;6(6):469-473. https://doi.org/10.1016/S0944-7113(00)80076-8
  8. Wen BY, Li JR. Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog. Zhongguo zhong yao za zhi. 2013;38(12):2015-8.
  9. Zhang L, Feng L, Jia Q, Xu J, Wang R, Wang Z, Wu Y, Li Y. Effects of b-glucosidase hydrolyzed products of harpagide and harpagoside on cyclooxygenase-2(COX-2) in vitro. Bioorganic & Medicinal Chemistry. 2011;19(16):4882-6. https://doi.org/10.1016/j.bmc.2011.06.069
  10. Stewart KM, Cole D. The commercial harvest of Devil's Claw (Harpagophytumspp.) in southern Africa: The devil's in the details. Journ of Ethnopharmacology. 2005; 100(3):225-236. https://doi.org/10.1016/j.jep.2005.07.004
  11. Mncwangi N, Chen W, Vermaak I, Viljoen AM, Gericke N. Devil's Claw-A review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens. Journal of Ethnopharmacol. 2012;143(3):755-771. https://doi.org/10.1016/j.jep.2012.08.013
  12. Costa de pasquale R, busa g, circoata c, lauk l, rarusa s, ficarra p, occhiuto f. A drug used in traditional medicine; harpagophytum procumbens dc. iii. Effects on hyperkinetic ventricular arrhythmias by reperfusion. Journal of Ethnopharmacol. 1985;13(2):193-9. https://doi.org/10.1016/0378-8741(85)90006-6
  13. ESCOP. Harpagophyti racix. Meppel: European scientific cooperative on phytotherapy. 1996.
  14. Jang MH, Lim S, Han SM, Park HJ, Shin JW, Kim NJ, Lee JS, Kim KA, Kim CJ. Harpagophytum Procumbens suppresses lipopolysaccharide-stimulated expressions of cyclooxygenase-2 and inducible nitric oxide synthase in fibroblast cell line L929. Journal of Pharmacol Sciences. 2003;93(3):367-371. https://doi.org/10.1254/jphs.93.367
  15. Fiebich BL, Heinrich M, Hiller KO, Kammerer N. Inhibition of TNF-alpha synthesis in LPS-stimulated primary human monocytes by Harpagophytum extract Stei-Hap69. Phytomedicine. 2001;8(1):28-30. https://doi.org/10.1078/0944-7113-00002
  16. Tippler B, Syrovets T, Plaza N, Loew D, Simmet T. Harpagophytum procumbens DC used in traditional medicine inhibits eicosanoid biosynthesis in human whole blood. International Journal of Tissue Reactions. 1997;19: 101-2.
  17. Loew D, Mollerfeld J, Schrodter A, Puttkammer S, Kaszkin M. Investigations on the pharmacokinetic properties of Harpagophytum extracts and their effects on eicosanoid biosynthesis in vitro and ex vivo. Clinical Pharmacology Therapeutics. 2001;69(5):356-364. https://doi.org/10.1067/mcp.2001.115445
  18. Whitehouse LW, Znamirowska M, Paul CJ. Devil's Claw (Harpagophytum procumbens): No evidence for anti-inflammatory activity in the treatment of arthritic disease. Canadian Medical Association Journal. 1983;129(3):249-251.
  19. 식품의약품안전청. 비임상시험관리기준. 식품의약품안전청고시 제2012-121호.
  20. 식품의약품안전청. 의약품등의 독성시험기준. 식품의약품안전청고시 제 2012-86호.
  21. 식품의약품안전청. 한약(생약)제제 비임상시험 가이드라인. 2014.
  22. 식품의약품안전청. 의약품등의 독성시험기준 해설서. 2012.
  23. Hachfeld B, Schippmann U. Conservation data sheet 2: Exploitation, trade and population status of Harpagophytum procumbens in southern Africa. Medicinal plant conservation. 2000;6:4-9
  24. Wichtl M. Herbal drugs and phytopharmaceuticals. Medpharm Scientific Publishers. Stuttgart. 2004;271-3
  25. Wyk BEV, Gericke N. People's Plants. A guide to Useful Plants of Southern Africa. Briza Publications, Pretoria. 2000.

Cited by

  1. A Case Report of Patients with Labrum Tear in Shoulder Treated by Oriental Therapy, Including Sinbaro3 Pharmacopuncture vol.33, pp.4, 2016, https://doi.org/10.13045/acupunct.2016066