DOI QR코드

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Subacute oral toxicity and bacterial mutagenicity study of Korean Red Ginseng oil

  • Seo, Hwi Won (Laboratory of Fundamental Research, Korea Ginseng Corporation) ;
  • Suh, Jae Hyun (Laboratory of Fundamental Research, Korea Ginseng Corporation) ;
  • So, Seung-Ho (Laboratory of Fundamental Research, Korea Ginseng Corporation) ;
  • Kyung, Jong-Soo (Laboratory of Fundamental Research, Korea Ginseng Corporation) ;
  • Kim, Yong-Soon (Korea Occupational Safety Health Research Institute) ;
  • Han, Chang-Kyun (Laboratory of Fundamental Research, Korea Ginseng Corporation)
  • 투고 : 2016.10.30
  • 심사 : 2017.01.17
  • 발행 : 2017.10.15

초록

Background: Red ginseng oil (RGO) is produced by supercritical $CO_2$ extraction of secondary products derived from Korean Red Ginseng extract. As the use of RGO has increased, product safety concerns have become more important. Methods: In the present study, the subacute oral toxicity and bacterial reverse mutagenicity of RGO were evaluated. Sprague-Dawley rats were orally administered with RGO for 28 d by gavage. Daily RGO dose concentrations were 0 mg/kg body weight (bw), 500 mg/kg bw, 1,000 mg/kg bw, or 2,000 mg/kg bw per day. Bacterial reverse mutation tests included five bacterial strains (Escherichia coli WP2 and Salmonella typhimurium TA98, TA100, TA1535, and TA1537), which were used in the presence or absence of metabolic activation. The plated incorporation method for mutation test was used with RGO concentrations ranging from $312.5{\mu}g$ to $5,000{\mu}g$ per plate. Results: The subacute oral toxicity test results did not reveal any marked changes in clinical characteristics. There were no toxicological changes related to RGO administration in hematological and serum biochemical characteristics in either control or treatment animals. Furthermore, no gross or histopathological changes related to RGO treatment were observed. The bacterial reverse mutation test results did not reveal, at any RGO concentration level and in all bacterial strains, any increase in the number of revertant colonies in the RGO treatment group compared to that in the negative control group. Conclusion: The no-observed-adverse-effect level of RGO is greater than 2,000 mg/kg bw and RGO did not induce genotoxicity related to bacterial reverse mutations.

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참고문헌

  1. Chan E, Tan M, Xin J, Sudarsanam S, Johnson DE. Interactions between traditional Chinese medicines and Western therapeutics. Curr Opin Drug Discov Devel 2010;13:50-65.
  2. Jordan SA, Cunningham DG, Marles R. Assessment of herbal medicinal products: Challenges, and opportunities to increase the knowledge base for safety assessment. Toxicol Appl Pharmacol 2010;243:198-216. https://doi.org/10.1016/j.taap.2009.12.005
  3. Zhou S, Chan E, Li SC, Huang M, Chen X, Li X, Zhang Q, Paxton JW. Predicting pharmacokinetic herb-drug interactions. Drug Metabol Drug Interact 2004;20:143-58.
  4. Choi RJ, Wong AST, Jia W, Chang IM, Wong RNS, Fan TP, Kim YS. Ginseng: a panacea linking East Asia and North America? Science 2015;350:S54-6.
  5. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, Shim JY, Kim M. An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol 2008;15:865-8. https://doi.org/10.1111/j.1468-1331.2008.02157.x
  6. Stavro PM, Woo M, Vuksan V. Korean red ginseng lowers blood pressure in individuals with hypertension. Am J Hypertens 2004;17:33A.
  7. Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean Red Ginseng. Mediat Inflamm 2012:732-860.
  8. Yun T-K, Zheng S, Choi S-Y, Cai SR, Lee Y-S, Liu XY, Cho KJ, Park KY. Non-organ-specific preventive effect of long-term administration of Korean Red Ginseng extract on incidence of human cancers. J Med Food 2010;13:489-94. https://doi.org/10.1089/jmf.2009.1275
  9. Ki SH, Yang JH, Ku SK, Kim SC, Kim YW, Cho IJ. Red ginseng extract protects against carbon tetrachloride-induced liver fibrosis. J Ginseng Res 2013;37:45-53. https://doi.org/10.5142/jgr.2013.37.45
  10. Lee SD, Yoo G, Chae HJ, In MJ, Oh NS, Hwang YK, Hwang WI, Kim DC. Lipid-soluble extracts as the main source of anticancer activity in ginseng and ginseng marc. J Am Oil Chem Soc 2009;86:1065. https://doi.org/10.1007/s11746-009-1460-x
  11. Yun J, Kim BG, Kang JS, Park SK, Lee K, Hyun DH, Kim HM, In MJ, Kim DC. Lipid-soluble ginseng extract inhibits invasion and metastasis of B16F10 melanoma cells. J Med Food 2015;18:102-8. https://doi.org/10.1089/jmf.2013.3138
  12. Bak MJ, Hong SG, Lee JW, Jeong WS. Red ginseng marc oil inhibits iNOS and COX-2 via $NF{\kappa}B$ and p38 pathways in LPS-stimulated RAW 264.7 macrophages. Molecules 2012;17:13769-86. https://doi.org/10.3390/molecules171213769
  13. Bak MJ, Jun M, Jeong WS. Antioxidant and hepatoprotective effects of the red ginseng essential oil in $H_2O_2$-treated HepG2 cells and CCl4-treated mice. Int J Mol Sci 2012;13:2314-30. https://doi.org/10.3390/ijms13022314
  14. Vlahakis C, Hazebroek J. Phytosterol accumulation in canola, sunflower, and soybean oils: effects of genetics, planting location, and temperature. J Am Oil Chem Soc 2000;77:49-53. https://doi.org/10.1007/s11746-000-0008-6
  15. Clark J. Tocopherols and sterols from soybeans. Lipid Technol 1996;8:111-4.
  16. Bak MJ, Kim KB, Jun M, Jeong WS. Safety of red ginseng oil for single oral administration in Sprague Dawley rats. J Ginseng Res 2014;38:78-81. https://doi.org/10.1016/j.jgr.2013.11.009
  17. OECD. Guidelines for testing of chemical. Repeated dose 28-day oral toxicity study in rodents (TG 407). 2008; OECD (Ed.).
  18. OECD. Guidelines for testing of chemical. Acute oral toxicity - acute toxic class method (TG 423). 2001; OECD (Ed.).
  19. Ruehl Fehlert C, Kittel B, Morawietz G, Deslex P, Keenan C, Mahrt CR, Nolte T, Robinson M, Stuart BP, Deschl U. Revised guides for organ sampling and trimming in rats and mice. Exp Toxic Pathol 2003;55:91-106.
  20. OECD. Guidelines for testing of chemical. Bacterial reverse mutation test (TG 471). 1997; OECD (Ed.).
  21. Ames B, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res 1975;31:347-64. https://doi.org/10.1016/0165-1161(75)90046-1
  22. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res 1983;113:173-215. https://doi.org/10.1016/0165-1161(83)90010-9
  23. Mortelmans K, Riccio ES. The bacterial tryptophan reverse mutation assay with Escherichia coli WP2. Mutat Res 2000;455:61-9. https://doi.org/10.1016/S0027-5107(00)00076-2
  24. Jeong MH, Yang K, Lee CG, Jeong DH, Park YS, Choi YJ, Kim JS, Oh SJ, Jeong SK, Jo WS. In vitro genotoxicity assessment of a novel resveratrol analogue, HS-1793. Toxicol Res 2014;30:211-20. https://doi.org/10.5487/TR.2014.30.3.211
  25. Reed DJ. Genetic toxicology: mutagenesis and adduct formation. In: Current protocols in toxicology. Wiley; 2005.
  26. Lee SD, Park SK, Lee ES, Kim HM, Lee CW, Lee K, Lee KH, Kan MR, Lee KS, Lee J, et al. A lipid-soluble red ginseng extract inhibits the growth of human lung tumor xenografts in nude mice. J Med Food 2010;13:1-5. https://doi.org/10.1089/jmf.2009.1142
  27. Li IC, Chen YL, Lee LY, Chen WP, Tsai YT, Chen CC, Chen CS. Evaluation of the toxicological safety of erinacine A-enriched Hericium erinaceus in a 28-day oral feeding study in Sprague-Dawley rats. Food Chem Toxicol 2014;70:61-7. https://doi.org/10.1016/j.fct.2014.04.040
  28. Patel SB, Rao NJ, Hingorani LL. Safety assessment of Withania somnifera extract standardized for Withaferin A: acute and sub-acute toxicity study. J Ayurveda Integr Med 2016;7:30-7. https://doi.org/10.1016/j.jaim.2015.08.001
  29. Traesel GK, de Souza JC, de Barros AL, Souza MA, Schmitz WO, Muzzi RM, Oesterreich SA, Arena AC. Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats. Food Chem Toxicol 2014;74:320-5. https://doi.org/10.1016/j.fct.2014.10.026
  30. Lee JM, Lee MA, Do HN, Song YI, Bae RJN, Lee HY, Park SH, Kang JS, Kang J. Historical control data from 13-week repeated toxicity studies in Crj:CD (SD) rats. Lab Anim Res 2012;28:115-21. https://doi.org/10.5625/lar.2012.28.2.115
  31. Edem DO. Palm oil: biochemical, physiological, nutritional, hematological, and toxicological aspects: a review. Plant Foods Hum Nutr 2002;l57:319-41.
  32. Estadella D, do Nascimento CM, Oyama LM, Ribeiro EB, Damaso AR, de Piano A. Lipotoxicity: effects of dietary saturated and transfatty acids. Mediat Inflamm 2013;137579:1-13.
  33. TomaW, Guimaraes LL, Brito A, Santos ARMS, Cortez FS, Pusceddu FH, Cesar A, Junior LS, Pacheco MTT, Pereira CDS. Safflower oil: an integrated assessment of phytochemistry, antiulcerogenic activity, and rodent and environmental toxicity. Rev Bras Farmacogn 2014;24:538-44. https://doi.org/10.1016/j.bjp.2014.09.004

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