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Subacute Oral Toxicity Study of Korean Red Ginseng Extract in Sprague-Dawley Rats

  • Park, Sang-Jin (Division of Non-clinical Studies, Korea Institute of Toxicology) ;
  • Lim, Kwang-Hyun (Division of Non-clinical Studies, Korea Institute of Toxicology) ;
  • Noh, Jeong-Ho (Division of Non-clinical Studies, Korea Institute of Toxicology) ;
  • Jeong, Eun Ju (Division of Non-clinical Studies, Korea Institute of Toxicology) ;
  • Kim, Yong-Soon (Botanical Drug Laboratory, R&D Headquarters, Korea Ginseng Corp.) ;
  • Han, Byung-Cheol (Botanical Drug Laboratory, R&D Headquarters, Korea Ginseng Corp.) ;
  • Lee, Seung-Ho (Botanical Drug Laboratory, R&D Headquarters, Korea Ginseng Corp.) ;
  • Moon, Kyoung-Sik (Division of Non-clinical Studies, Korea Institute of Toxicology)
  • Received : 2013.10.28
  • Accepted : 2013.12.23
  • Published : 2013.12.31

Abstract

Ginseng is a well-known traditional medicine used in Asian countries for several thousand years, and it is currently applied to medicine, cosmetics, and nutritional supplements due to its many healing and energygiving properties. It is well demonstrated that ginsenosides, the main ingredient of ginseng, produce a variety of pharmacological and therapeutic effects on central nerve system (CNS) disorders, cardiovascular disease, endocrine secretions, aging, and immune function. Korean red ginseng extract is a dietary supplement containing ginsenoside Rb1 and ginsenoside Rg1 extracted from Panax ginseng. While the pharmacokinetics and bioavailability of the extract have been well established, its toxicological properties remain obscure. Thus, four-week oral toxicity studies in rats were conducted to investigate whether Korean red ginseng extract could have a potential toxicity to humans. The test article was administered once daily by oral gavage to four groups of male and female Sprague-Dawley (SD) rats at dose levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. Neither deaths nor clinical symptoms were observed in any group during the experiment. Furthermore, no abnormalities in body weight, food consumption, ophthalmology, urinalysis, hematology, serum biochemistry, gross findings, organ weights, or histopathology were revealed related to the administration of the test article in either sex of any dosed group. Therefore, a target organ was not determined in this study, and the no observed adverse effect level (NOAEL) of Korean red ginseng extract was established to be 2,000 mg/kg/day.

Keywords

References

  1. Chandler, R.F. (1988) Ginseng-aphrodisiac. Can. Pharm. J., 121, 36-38.
  2. Liu, C.X. and Xiao, P.G. (1992) Recent advances on ginseng research in China. J. Ethnopharmacol., 36, 27-38. https://doi.org/10.1016/0378-8741(92)90057-X
  3. Seong, Y.H., Shin, C.S., Kim, H.S. and Baba, A. (1995) Inhibitory effects of ginseng total saponins on glutamate-induced swelling of cultured astrocytes. Biol. Pharm. Bull., 18, 1776-1778. https://doi.org/10.1248/bpb.18.1776
  4. Kitts, D.D., Wijewickreme, A.N. and Hu, C. (2000) Antioxidant properties of a North American ginseng extract. Mol. Cell. Biochem., 203, 1-10. https://doi.org/10.1023/A:1007078414639
  5. Buettner, C., Yeh, G.Y., Phillips, R.S., Mittleman, M.A. and Kaptchuk, T.J. (2006) Systematic review of the effects of ginseng on cardiovascular risk factors. Ann. Pharmacother., 40, 83-95. https://doi.org/10.1345/aph.1G216
  6. Joo, S.S., Yoo, Y.M., Ahn, B.W., Nam, S.Y., Kim, Y.B., Hwang, K.W. and Lee, D.I. (2008) Prevention of inammation-mediated neurotoxicity by Rg3 and its role in microglial activation. Biol. Pharm. Bull., 31, 1392-1396. https://doi.org/10.1248/bpb.31.1392
  7. Baek, N.I., Kim, D.S., Lee, Y.H., Park, J.D., Lee, C.B. and Kim, S.I. (1996) Ginsenoside Rh4, a genuine dammarane glycoside from Korean red ginseng. Planta Med., 62, 86-87. https://doi.org/10.1055/s-2006-957816
  8. Wang, A., Wang, C.Z., Wu, J.A., Osinski, J. and Yuan, C.S. (2005) Determination of major ginsenosides in Panax quinquefolius (American ginseng) using highperformance liquid chromatography. Phytochem. Anal., 16, 272-277. https://doi.org/10.1002/pca.838
  9. Lim, W., Mudge, K.W. and Vermeylen, F. (2005) Effects of population, age, and cultivation methods on ginsenoside content of wild American ginseng (Panax quinquefolium). J. Agric. Food Chem., 53, 8498-8505. https://doi.org/10.1021/jf051070y
  10. Shibata, S. (2001) Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Korean Med. Sci., 16, S28-37. https://doi.org/10.3346/jkms.2001.16.S.S28
  11. Shen, Y.J. (2000) Pharmacology of Traditional Chinese Medicine. Renmin Weisheng Press, Beijing, pp. 1-200.
  12. Nocerino, E., Amato, M. and Izzo, A.A. (2000) The aphrodisiac and adaptogenic properties of ginseng. Fitoterapia, 71, S1-5. https://doi.org/10.1016/S0367-326X(00)00170-2
  13. Cui, Y., Shu, X.O., Gao, Y.T., Cai, H., Tao, M.H. and Zheng, W. (2006) Association of ginseng use with survival and quality of life among breast cancer patients. Am. J. Epidemiol., 163, 645-653. https://doi.org/10.1093/aje/kwj087
  14. Xu, Q.F., Fang, X.L. and Chen, D.F. (2003) Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J. Ethnopharmacol., 84, 187-192. https://doi.org/10.1016/S0378-8741(02)00317-3
  15. Ryu, M.H. and Cha, Y.S. (2003) The effects of a high-fat or high-sucrose diet on serum lipid profiles, hepaticacyl-CoA synthetase, carnitine palmitoyltransferase-I, and the acetyl-CoA. carboxylase mRNA levels in rats. J. Biochem. Mol. Biol., 36, 312-318. https://doi.org/10.5483/BMBRep.2003.36.3.312
  16. Gaysinskaya, V.A., Karatayev, O., Chang, G.Q. and Leibowitz, S.F. (2007) Increased caloric intake after a high-fat preload: Relation to circulating triglycerides and orexigenic peptides. Physiol. Behav., 91, 142-153. https://doi.org/10.1016/j.physbeh.2007.02.002
  17. Siegel, R.K. (1979) Ginseng abuse syndrome. Problems with the panacea. JAMA, 241, 1614-1615. https://doi.org/10.1001/jama.1979.03290410046024
  18. Hess, F.G. Jr., Parent, R.A., Cox, G.E., Stevens, K.R. and Becci, P.J. (1982) Reproduction study in rats or ginseng extract G115. Food Chem. Toxicol., 20, 189-192. https://doi.org/10.1016/S0278-6915(82)80246-9
  19. Popov, I.M. and Goldwag, W.J. (1973) A review of the properties and clinical effects of ginseng. Am. J. Chin. Med., 1, 263-270. https://doi.org/10.1142/S0192415X73000280
  20. Bittles, A.H., Fulder, S.J., Grant, E.C. and Nicholls, M.R. (1979) The effect of ginseng on life-span and stress responses in mice. Gerontology, 25, 125-131. https://doi.org/10.1159/000212330
  21. Hess, F.G. Jr., Parent, R.A., Stevens, K.R., Cox, G.E. and Becci, P.J. (1983) Effects of subchronic feeding of ginseng extract G115 in beagle dogs. Food Chem. Toxicol., 21, 95-97. https://doi.org/10.1016/0278-6915(83)90275-2

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