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Assessment of the Toxicity and the Stability of Saeng Mak San by Using Repeated Intravenous Injections in Sprague-Dawley Rats

  • Lee, Hwa-Young (Department of Neuropsychiatry, Hospital of Korean Medicine, Kyung-Hee University Medical Center, Kyung-Hee University) ;
  • Kim, Sungchul (ALS/MND Center of Wonkwang University) ;
  • Cho, Seung-Hun (Department of Neuropsychiatry, Hospital of Korean Medicine, Kyung-Hee University Medical Center, Kyung-Hee University)
  • Received : 2015.12.31
  • Accepted : 2016.08.02
  • Published : 2016.09.30

Abstract

Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS. Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.

Acknowledgement

Supported by : Kyung-Hee University

References

  1. Korean pharmacopuncture institute. [Pharmacopuncture therapy guidelines]. Seoul: Hansung printing; 1999. 143 p. Korean.
  2. Joo HJ. [Researches on pharmacopuncture]. Korea Institute of Oriental medicine. 1995;5:193-210. Korean.
  3. Konishi T. Brain oxidative stress as basic target of antioxidant traditional oriental medicines. Neurochem Res. 2009;34(4):711-6. https://doi.org/10.1007/s11064-008-9872-9
  4. Chen CY, Lu LY, Chen P, Ji KT, Lin JF, Yang PL, et al. Shengmai injection, a traditional Chinese patent medicine, for intradialytic hypotension: a systematic review and meta-analysis. Evid Based Complement Alternat Med. 2013;2013:ID703815.
  5. Zhang YC, Chen RM, Lu BJ, Rong YZ. Effect of shengmai injection on cardiac function and inflammatory reaction in patients with acute coronary syndrome. Chin J Integr Med. 2008;14(2):107-10. https://doi.org/10.1007/s11655-008-0107-3
  6. Leong PK, Chen N, Chiu PY, Leung HY, Ma CW, Tang QT, et al. Long-term treatment with shengmai san-derived herbal supplement (Wei Kang Su) enhances antioxidant response in various tissues of rats with protection against carbon tetrachloride hepatotoxicity. J Med Food. 2010;13(2):427-38. https://doi.org/10.1089/jmf.2009.1296
  7. Wang L, Nishida H, Ogawa Y, Konishi T. Prevention of oxidative injury in PC12 cells by a traditional Chinese medicine, Shengmai San, as a model of an antioxidant- based composite formula. Biol Pharm Bull. 2003;26(7):1000-4. https://doi.org/10.1248/bpb.26.1000
  8. Nishida H, Kushida M, Nakajima Y, Ogawa Y, Tatewaki N, Sato S, et al. Amyloid-beta-induced cytotoxicity of PC-12 cell was attenuated by Shengmai-san through redox regulation and outgrowth induction. J Pharmacol Sci. 2007;104(1):73-81. https://doi.org/10.1254/jphs.FP0070100
  9. Yu JH, Guo HW, Liu MM. [Impact of shengmal injection on changes of immunological function in patients after cardiopulmonary bypass]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2009;29(4):317-21. Chinese.
  10. Zhou Q, Qin WZ, Liu SB, Kwong JS, Zhou J, Chen J. Shengmai (a traditional Chinese herbal medicine) for heart failure. Cochrane Database Syst Rev. 2014;14(4):CD005052.
  11. Wang NL, Chang CK, Liou YL, Lin CL, Lin MT. Shengmai San, a Chinese herbal medicine protects against rat heat stroke by reducing inflammatory cytokines and nitric oxide formation. J Pharmacol Sci. 2005;98(1):1-7. https://doi.org/10.1254/jphs.FP0050018
  12. Seo TB, Baek K, Kwon KB, Lee SI, Lim JS, Seol IC, et al. Shengmai-san-mediated enhancement of regenerative responses of spinal cord axons after injury in rats. J Pharmacol Sci. 2009;110(4):483-92. https://doi.org/10.1254/jphs.09044FP