Lab Anim Res.  2014 Sep;30(3):104-111. 10.5625/lar.2014.30.3.104.

Evaluation of the genotoxicity of ginseng leaf extract UG0712

Affiliations
  • 1Laboratory of Genetic Toxicology, Korea Institute of Toxicology, KRICT, Daejeon, Korea.
  • 2Department of Histology, College of Veterinary Medicine, Kyungpook National University, 1370 Sankyuk-dong, Bukgu, Daegu, Korea. psj26@knu.ac.kr
  • 3Unigen Inc., Cheonan, Korea.

Abstract

Although ginseng (genus Panax) leaf extract contains high concentrations of bioactive constituents, its effects have been reported in few preclinical studies, and information regarding its toxicity is not sufficient to allow for its clinical use. We evaluated the genotoxicity of UG0712, which is a powdered extract of ginseng leaves. UG0712 did not increase the number of revertant colonies in 4 histidine auxotrophic strains of Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) or in a tryptophan auxotrophic strain of Escherichia coli (WP2uvrA(pKM101)) at any concentration evaluated, either in the absence or presence of the metabolic activation system. There was no significant increase in the number of metaphase cells with structural or numerical aberrations in the UG0712-treated groups compared to the concurrent vehicle control at any dose, regardless of the presence of the metabolic activation system. Oral administration of the extract at doses up to 2,000 mg/kg in male mice did not increase the frequency of micronucleated polychromatic erythrocytes in the bone marrow, and did not result in any significant clinical signs, body weight loss, gross findings, or mortality. These results suggest that UG0712 does not act as a mutagenic or genotoxic material at the concentrations evaluated.

Keyword

UG0712; ginseng leaf extract; bacterial reverse mutation; chromosome aberration; micronucleus

MeSH Terms

Administration, Oral
Animals
Biotransformation
Body Weight
Bone Marrow
Chromosome Aberrations
Erythrocytes
Escherichia coli
Histidine
Humans
Male
Metaphase
Mice
Mortality
Panax*
Salmonella typhimurium
Tryptophan
Histidine
Tryptophan

Figure

  • Figure 1 UG0712 dose-response curve for revertant colonies in the presence of the metabolic activation system. Five test strains (S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2uvrA) were exposed to UG0712 and incubated for 48 h. Data were expressed as the mean values of colonies from 3 plates for each concentration. * is growth inhibition.


Reference

1. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999; 58(11):1685–1693. PMID: 10571242.
2. Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacol Sin. 2005; 26(2):143–149. PMID: 15663889.
Article
3. Shin HR, Kim JY, Yun TK, Morgan G, Vainio H. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control. 2000; 11(6):565–576. PMID: 10880039.
4. Wang H, Peng D, Xie J. Ginseng leaf-stem: bioactive constituents and pharmacological functions. Chin Med. 2009; 4:20. PMID: 19849852.
Article
5. Cheng TO. Panax (ginseng) is not a panacea. Arch Intern Med. 2000; 160(21):3329. PMID: 11088100.
Article
6. Wang Z, Zheng Q, Liu K, Li G, Zheng R. Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol. 2006; 98(4):411–415. PMID: 16623867.
Article
7. Lee FC. Facts About Ginseng: The Elixir of Life. Hollym International Corporation;1992.
8. Qi X, Ignatova S, Luo G, Liang Q, Jun FW, Wang Y, Sutherland I. Preparative isolation and purification of ginsenosides Rf, Re, Rd and Rb1 from the roots of Panax ginseng with a salt/containing solvent system and flow step-gradient by high performance counter-current chromatography coupled with an evaporative light scattering detector. J Chromatogr A. 2010; 1217(13):1995–2001. PMID: 20171644.
Article
9. Raghavendran HR, Sathyanath R, Shin J, Kim HK, Han JM, Cho J, Son CG. Panax ginseng modulates cytokines in bone marrow toxicity and myelopoiesis: ginsenoside Rg1 partially supports myelopoiesis. PLoS One. 2012; 7(4):e33733. PMID: 22523542.
Article
10. Ceylan-Isik AF, Fliethman RM, Wold LE, Ren J. Herbal and traditional Chinese medicine for the treatment of cardiovascular complications in diabetes mellitus. Curr Diabetes Rev. 2008; 4(4):320–328. PMID: 18991600.
Article
11. Hou JP. The chemical constituents of ginseng plants. Comp Med East West. 1977; 5(2):123–145. PMID: 608333.
Article
12. Zhang QH, Wu CF, Duan L, Yang JY. Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol. 2008; 46(1):293–302. PMID: 17904265.
Article
13. Xie JT, Mehendale SR, Wang A, Han AH, Wu JA, Osinski J, Yuan CS. American ginseng leaf: ginsenoside analysis and hypoglycemic activity. Pharmacol Res. 2004; 49(2):113–117. PMID: 14643691.
Article
14. KFDA. Testing Guidelines for Safety Evaluation of Drugs (Notification No. 2014-136) issued by the Korea Food and Drug Administration. 2014.
15. OECD. Guideline for Testing of Chemicals, Section 4, Health Effects, No. 471. 1997.
16. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res. 1983; 113(3-4):173–215. PMID: 6341825.
Article
17. OECD. Guideline for Testing of Chemicals, Section 4, Health Effects, No. 473. 1997.
18. Ishidate M Jr. Data book of chromosomal aberration test in vitro. Elsevier;1998.
19. Ishidate M Jr, Odashima S. Chromosome tests with 134 compounds on Chinese hamster cells in vitro--a screening for chemical carcinogens. Mutat Res. 1977; 48(3-4):337–353. PMID: 876270.
20. Sofuni T, Matsuoka A, Sawada M, Ishidate M Jr, Zeiger E, Shelby MD. A comparison of chromosome aberration induction by 25 compounds tested by two Chinese hamster cell (CHL and CHO) systems in culture. Mutat Res. 1990; 241(2):175–213. PMID: 2345556.
Article
21. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55–63. PMID: 6606682.
Article
22. OECD. Guideline for Testing of Chemicals, Section 4, Health Effects, No. 474. 1997.
23. Hayashi M, MacGregor JT, Gatehouse DG, Adler ID, Blakey DH, Dertinger SD, Krishna G, Morita T, Russo A, Sutou S. In vivo rodent erythrocyte micronucleus assay. II. Some aspects of protocol design including repeated treatments, integration with toxicity testing, and automated scoring. Environ Mol Mutagen. 2000; 35(3):234–252. PMID: 10737958.
Article
24. Schmid W. The micronucleus test. Mutat Res. 1975; 31(1):9–15. PMID: 48190.
Article
25. Kastenbaum MA, Bowman KO. Tables for determining the statistical significance of mutation frequencies. Mutat Res. 1970; 9(5):527–549. PMID: 5424720.
Article
26. Ben-Hur E, Fulder S. Effect of Panax ginseng saponins and Eleutherococcus senticosus on survival of cultured mammalian cells after ionizing radiation. Am J Chin Med. 1981; 9(1):48–56. PMID: 7304498.
Article
27. Keum YS, Han SS, Chun KS, Park KK, Park JH, Lee SK, Surh YJ. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression, NF-kappaB activation and tumor promotion. Mutat Res. 2003; 523-524:75–85. PMID: 12628505.
28. Liu WK, Xu SX, Che CT. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci. 2000; 67(11):1297–1306. PMID: 10972198.
Article
29. Ong YC, Yong EL. Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity. Ann Acad Med Singapore. 2000; 29(1):42–46. PMID: 10748963.
30. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull. 1995; 18(9):1197–1202. PMID: 8845804.
Article
31. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS. Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine. 2003; 10(6-7):600–605. PMID: 13678250.
Article
32. Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS, Yuan CS. Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes. 2002; 51(6):1851–1858. PMID: 12031973.
Article
33. Xie JT, Zhou YP, Dey L, Attele AS, Wu JA, Gu M, Polonsky KS, Yuan CS. Ginseng berry reduces blood glucose and body weight in db/db mice. Phytomedicine. 2002; 9(3):254–258. PMID: 12046868.
Article
34. Wang BX, Cui JC, Liu AJ. The action of ginsenosides extracted from the stems and leaves of Panax ginseng in promoting animal growth. Yao Xue Xue Bao. 1982; 17(12):899–904. PMID: 7183121.
35. EMEA/HMPC/107079, Guideline on the Assessment of Genotoxicity of Herbal Substances/Preparations. 2007.
36. Abdelmigid HM. Sivakumar Gowder, editor. New Trends in genotoxicity testing of herbal medicinal plants, New Insights into Toxicity and Drug Testing. 2013. (ISBN: 978-953-51-0946-4, InTech, DOI: 10.5772/54858. Available from: http://www.intechopen.com/books/new-insights-into-toxicity-and-drug-testing/new-trends-in-genotoxicity-testing-of-herbal-medicinal-plants).
37. Tinwell H, Ashby J. Comparison of acridine orange and Giemsa stains in several mouse bone marrow micronucleus assays--including a triple dose study. Mutagenesis. 1989; 4(6):476–481. PMID: 2695763.
Article
Full Text Links
  • LAR
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr