Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

Single-Dose Intramuscular Toxicity Test Using No-Pain Pharmacopuncture in Sprague-Dawley Rats

  • Ji Hye, Hwang (Department of Acupuncture and Moxibustion Medicine, College of Korean Medicine, Gachon University) ;
  • Chul, Jung (Namsangcheon Korean Medicine Clinic)
  • Received : 2023.01.05
  • Accepted : 2023.03.08
  • Published : 2023.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: This study aimed to evaluate the potential toxicity of a recently developed and clinically used No-Pain pharmacopuncture (NPP) solution. We also assessed the lethal dose of the NPP agent following a single intramuscular injection in Sprague-Dawley (SD) rats. Methods: Animals were divided into two groups: the NPP test material group and the normal saline control group. A single intramuscular injection of the NPP agent (1.0 mL/animal) was administered to rats of the NPP test material group. The control group rats received the same volume of normal saline. Both female and male rats were included in each group. All rats were monitored for clinical signs and body weight changes for 14 days after administration of the test substance or saline. At the end of the observation period, a gross necropsy was conducted and localized tolerance at the injection site was analyzed. Results: No mortality was observed in the NPP test material and control groups. Moreover, no test substance-related effects were observed on clinical signs, body weight, necropsy findings, and localized tolerance at the injection site. Conclusion: The approximate lethal dose of the NPP agent is greater than 1.0 mL/animal under the conditions used in this study. Additional toxicity evaluations and clinical studies are needed to confirm the safety of NPP use in clinical practice.

Keywords

Acknowledgement

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-2022R1A2C1013518).

References

  1. Ardalan MR, Rafieian-Kopaei M. Is the safety of herbal medicines for kidneys under question? J Nephropharmacol. 2013;2(2):11-2. 
  2. Hwang JH, Ku J, Jung C. Genotoxicity evaluation of capsaicin-containing (CP) pharmacopuncture, in an in vivo micronucleus test. J Pharmacopuncture. 2020;23(4):237-46.  https://doi.org/10.3831/KPI.2020.23.4.237
  3. Ministry of Food and Drug Safety. (Herbal Medicine) Regulation on Approval and Notification of Herbal (crude) Medicinal Preparations, Etc [Internet]. Cheongju: Ministry of Food and Drug Safety; 2022 [cited 2022 Dec 1]. Available from: https://www.law.go.kr/%ED%96%89%EC%A0%95%EA%B7%9C%EC%B9%99/%ED%95%9C%EC%95%BD(%EC%83%9D%EC%95%BD)%EC%A0%9C%EC%A0%9C%20%EB%93%B1%EC%9D%98%20%ED%92%88%EB%AA%A9%ED%97%88%EA%B0%80%C2%B7%EC%8B%A0%EA%B3%A0%EC%97%90%20%EA%B4%80%ED%95%9C%20%EA%B7%9C%EC%A0%95. 
  4. Wiebrecht A, Kalg A. Letter: Herbal hepatotoxicity--an update on traditional Chinese medicine preparations. Aliment Pharmacol Ther. 2014;40(6):737-8.  https://doi.org/10.1111/apt.12883
  5. Kim EJ, Chen Y, Huang JQ, Li KM, Razmovski-Naumovski V, Poon J, et al. Evidence-based toxicity evaluation and scheduling of Chinese herbal medicines. J Ethnopharmacol. 2013;146(1):40-61.  https://doi.org/10.1016/j.jep.2012.12.027
  6. Zhou J, Ouedraogo M, Qu F, Duez P. Potential genotoxicity of traditional chinese medicinal plants and phytochemicals: an overview. Phytother Res. 2013;27(12):1745-55.  https://doi.org/10.1002/ptr.4942
  7. Ministry of Food and Drug Safety. Good Laboratory Practice (GLP) [Internet]. Cheongju: Ministry of Food and Drug Safety; 2017 [cited 2022 Apr 1]. Available from: https://www.law.go.kr/LSW/admRulInfoP.do?admRulSeq=2100000086689. 
  8. Ministry of Food and Drug Safety. Partial Amendment Official Announcement about Toxicity Test for Drug [Internet]. Cheongju: Ministry of Food and Drug Safety; 2015 Nov 10 [updated 2015 Nov 11; cited 2022 Nov 11]. Available from: https://www.law.go.kr/LSW/admRulLsInfoP.do?chrClsCd=010202&admRulSeq=2100000032147. 
  9. Lee MY, Seo CS, Kim JY, Shin HK. Genotoxicity evaluation of Guibi-Tang extract using an in vitro bacterial reverse mutation assay, chromosome aberration assay, and in vivo micronucleus test. BMC Complement Altern Med. 2014;14:215. 
  10. Jeong JH, Ku J, Hwang JH. A study on the significance of acupuncture and pharmacopuncture therapy for cold accumulation through a literature review on the historical development process in cold accumulation treatment. J Acupunct Res. 2022;39(4):267-74.  https://doi.org/10.13045/jar.2022.00178
  11. Korean Acupuncture and Moxibustion Society. Acupuncture medicine. Seoul: Hanmi Medical Publishing Co; 2020. 
  12. Sung SH, Shin BC, Park MJ, Kim KH, Kim JW, Ryu JY, et al. Current status of management on pharmacopuncture in Korea through introduction of an accreditation system. J Pharmacopuncture. 2019;22(2):75-82.  https://doi.org/10.3831/KPI.2019.22.009
  13. Park J, Lee H, Shin BC, Lee MS, Kim B, Kim JI. Pharmacopuncture in Korea: a systematic review and meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2016;2016:4683121. 
  14. Park JE, Kim KH, Kang S, Lee EK, Kim JC, Jang BH, et al. Usage status and satisfaction with pharmacopuncture in Korea: a survey among Korean medicine doctors. Eur J Integr Med. 2019;27:121-30.  https://doi.org/10.1016/j.eujim.2019.03.001
  15. Hwang JH, Ku J, Jung C. Single-dose intramuscular toxicity study of SU-Eohyeol pharmacopuncture in rats. J Pharmacopuncture. 2022;25(3):268-75.  https://doi.org/10.3831/KPI.2022.25.3.268
  16. Park JE. A survey on Korean medicine doctor's use of Herbal Acupuncture and recognition of its national health insurance coverage [master's thesis]. [Seoul]: Kyung Hee University; 2018. 68 p. 
  17. Tian B, Tian M, Huang SM. Advances in phytochemical and modern pharmacological research of Rhizoma Corydalis. Pharm Biol. 2020;58(1):265-75.  https://doi.org/10.1080/13880209.2020.1741651
  18. Li B, Xu X, Wang X, Yu H, Li X, Tao W, et al. A systems biology approach to understanding the mechanisms of action of Chinese herbs for treatment of cardiovascular disease. Int J Mol Sci. 2012;13(10):13501-20.  https://doi.org/10.3390/ijms131013501
  19. Takao Y, Takaoka Y, Sugano A, Sato H, Motoyama Y, Ohta M, et al. Shakuyaku-kanzo-to (Shao-Yao-Gan-Cao-Tang) as treatment of painful muscle cramps in patients with lumbar spinal stenosis and its minimum effective dose. Kobe J Med Sci. 2015;61(5):E132-7. 
  20. Kim M, Kim HS, Kim JH, Kim EY, Lee B, Lee SY, et al. Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis. BMC Complement Med Ther. 2020;20(1):35. 
  21. Herbology Editorial Committee of Korean Medicine. Herbology. Seoul: Younglimsa; 2004. 
  22. Wang L, Zhang Y, Wang Z, Gong N, Kweon TD, Vo B, et al. The antinociceptive properties of the Corydalis yanhusuo extract. PLoS One. 2016;11(9):e0162875. 
  23. Chinese Pharmacopoeia Commission (CPC). Pharmacopoeia of the People's Republic of China. Vol. 1. Beijing: China Medical Science Press; 2015. 
  24. Ahn CJ, Ahn BC, Park DS. The analgesic effect of aqua-acupuncture with Corydalis Tuber, Olibanum Mastix & Myrrha. J Korean Acupunct Moxib Med Soc. 1994;11(1):145-58. 
  25. Ahn HS, Park YB, Kang SK. Effects of Corydalis Tuber Aqua-acupuncture on the pain and convulsion in mice and gastric ulcer in rats. J Korean Acupunct Moxib Med Soc. 1994;11(1):99-111. 
  26. Choi WY, Park SJ, Lee JR, Jegal K, Kim YW, Byun SH, et al. Modulation of inflammatory mediators by corydalis tuber in LPS-stimulated Raw264.7 cells and its inhibitory effects on carrageenan-stimulated paw edema in rats. Orient Pharm Exp Med. 2014;14(4):319-28.  https://doi.org/10.1007/s13596-014-0153-7
  27. Yoon SJ, Kim YS. Effect of Corydalidis Tuber.Carthami Flos.Paeoniae Radix Rubra on anti-inflamation and function of the liver at arthritis rats. Korean J Orient Physiol Pathol. 2005;19(2):475-80. 
  28. Kang JH, Heo DS, Yoon IJ, Oh MS. An analysis of tendencies of studies on herbal acupuncture - focusing on domestic theses since 2001 about anti-inflammation, pain relief and anti-obesity effects, including safety. J Korean Orient Med. 2007;28(2):93-113. 
  29. Kim HJ, Jeon JH, Kim YI. A study on the effect of Erycibae Caulis and Corydalis Tuber Pharmacopuncture on a mouse model with collagen induced rheumatoid arthritis. The Acupuncture. 2016;33(2):21-34.  https://doi.org/10.13045/acupunct.2016014
  30. Yoon JW, Kim SJ. A review of clinical study on Jungsongouhyul pharmacopuncture treatment published in Korea. J Korean Med Rehabi. 2017;27(4):75-84.  https://doi.org/10.18325/jkmr.2017.27.4.75
  31. Chen Q, Wei W. Effects and mechanisms of glucosides of chaenomeles speciosa on collagen-induced arthritis in rats. Int Immunopharmacol. 2003;3(4):593-608.  https://doi.org/10.1016/S1567-5769(03)00051-1
  32. Kwon K, Park KC, Sohn SH, Park HS. The experimental study on Chaenomelis Fructus (木瓜) in case of the arthritis induced by injecting Freund's complete adjuvant. J Pharmacopunct. 2003;6(2):29-43.  https://doi.org/10.3831/KPI.2003.6.2.029
  33. Hyodo T, Taira T, Takemura T, Yamamoto S, Tsuchida M, Yoshida K, et al. Immediate effect of Shakuyaku-kanzo-to on muscle cramp in hemodialysis patients. Nephron Clin Pract. 2006;104(1):c28-32.  https://doi.org/10.1159/000093256
  34. Blyton F, Chuter V, Walter KE, Burns J. Non-drug therapies for lower limb muscle cramps. Cochrane Database Syst Rev. 2012;1(1):CD008496.