Korean Journal of Oriental Medicine (한국한의학연구원논문집)

Korean Institute of Oriental Medicine (한국한의학연구원)
권호 표지

Micronucleus Test of Bupleuri Radix Aqueous Extract in Bone Marrow Cells of Male ICR Mice

시호 물 추출물의 마우스 골수세포를 이용한 유전독성 평가

  • Cheon, Woo-Hyun (College of Oriental Medicine, Daegu Haany University) ;
  • Chung, In-Kwon (College of Oriental Medicine, Daegu Haany University) ;
  • Kang, Su-Jin (The Medical Research center for Globalization of Herbal Formulation, Daegu Haany University) ;
  • Ku, Sae-Kwang (College of Oriental Medicine, Daegu Haany University) ;
  • Lee, Young-Joon (College of Oriental Medicine, Daegu Haany University)
  • 전우현 (대구한의대학교 한의과대학) ;
  • 정인권 (대구한의대학교 한의과대학) ;
  • 강수진 (대구한의대학교 방제과학 글로벌 연구센터) ;
  • 구세광 (대구한의대학교 한의과대학) ;
  • 이영준 (대구한의대학교 한의과대학)
  • Received : 2012.04.17
  • Accepted : 2012.07.20
  • Published : 2012.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

In this research, the genotoxic effect of Bupleuri Radix (BR), the dried roots of Bupleurum falcatum Linne has been traditionally used as anti-inflammatory agent, was evaluated using the mouse micronucleus test. BR aqueous extract (yield = 16.52%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide (CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p<0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of BR extracts treated mice with over 0.30 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that BR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels the limit dosage in rodents.

Keywords

References

  1. Lee JE, Kim HJ, Choi EK, Chai HY, Yun YW, Kim DJ, Nam SY, Lee BJ, Ahn BW, Kang HG, Kim YB. Four-week repeated-dose toxicity study on Pinellia Extract. Korean J Lab Anim Sci. 2003;19:127-141.
  2. Chung IK, Cheon WH, Ku SK. Micronucleus test of Picrorrhiza Rhizoma aqueous extract in bone marrow cells of male ICR mice. Toxicol Res. 2011;27:119-123. https://doi.org/10.5487/TR.2011.27.2.119
  3. Renner HW. In vivo effects of single or combined dietary antimutagens on mutagen-induced chromosomal aberrations. Mutat Res. 1990;244(2):185-188. https://doi.org/10.1016/0165-7992(90)90070-Z
  4. Korea Food and Drug Administration. Testing Guidelines for Safety Evaluation of Drugs, 2009-116 (2009).
  5. Kalantari H, Larki A, Latifi SM. The genotoxicity study of garlic and pasipy herbal drops by peripheral blood micronucleus test. Acta Physiol Hung. 2007;94(3):261-266. https://doi.org/10.1556/APhysiol.94.2007.3.10
  6. Roh SS, Lee HS, Ku SK. Micronucleus test of DHU001, a polyherbal formula, in bone marrow cells of male ICR mice. Toxicol Res. 2009;25:225-230. https://doi.org/10.5487/TR.2009.25.4.225
  7. Lee B, Shim I, Lee H, Hahm DH. Effect of Bupleurum falcatum on the stress-induced impairment of spatial working memory in rats. Biol Pharm Bull. 2009;32(8):1392-1398. https://doi.org/10.1248/bpb.32.1392
  8. Cho BS, Kim SD, Park JK, Chung JH, Hong MS, Lee BC, Ihm CG. Effects of Bupleurum falcatum and its combination with an angiotensin II receptor blocker on cytokine and chemokine expression in human mesangial cells. Phytother Res. 2010;24(3):339-343. https://doi.org/10.1002/ptr.2936
  9. Yamamoto M, Kumagai A, Yamamura Y. Structure and actions of saikosaponins isolated from Bupleurum falcatum L. I. Anti-inflammatory action of saikosaponins. Arzneimittel-Forschung. 1975;25(7):1021-1023.
  10. Yamamoto M, Kumagai A, Yamamura Y. Structure and action of saikosaponins isolated from Bupleurum falcatum L. II. Metabolic actions of saikosaponins, especially a plasma cholesterol-lowering action. Arzneimittel-Forschung. 1975;25(8):1240-1243.
  11. Abe H, Sakaguchi M, Yamada M, Arichi S, Odashima S. Pharmacological actions of saikosaponins isolated from Bupleurum falcatum. 1. Effects of saikosaponins on liver function. Planta medica. 1980;40(4):366-372.
  12. Lin CC, Chiu HF, Yen MH, Wu CC, Chen MF. The pharmacological and pathological studies on Taiwan folk medicine (III): The effects of bupleurum kaoi and cultivated bupleurum falcatum var. komarowi. The American journal of Chinese medicine. 1990;18(3-4):105-112.
  13. Hattori T, Ito M, Suzuki Y. [Studies on antinephritic effects of plant components in rats (1). Effects of saikosaponins original-type anti-GBM nephritis in rats and its mechanisms]. Nihon yakurigaku zasshi Folia pharmacologica Japonica. 1991;97(1):13-21. https://doi.org/10.1254/fpj.97.1_13
  14. Sakurai MH, Matsumoto T, Kiyohara H, Yamada H. B-cell proliferation activity of pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L. and its structural requirement. Immunology. 1999; 97(3):540-547. https://doi.org/10.1046/j.1365-2567.1999.00774.x
  15. Guo Y, Matsumoto T, Kikuchi Y, Ikejima T, Wang B, Yamada H. Effects of a pectic polysaccharide from a medicinal herb, the roots of Bupleurum falcatum L. on interleukin 6 production of murine B cells and B cell lines. Immunopharmacology. 2000;49(3):307-316. https://doi.org/10.1016/S0162-3109(00)00245-9
  16. Matsumoto T, Sun XB, Hanawa T, Kodaira H, Ishii K, Yamada H. Effect of the antiulcer polysaccharide fraction from Bupleurum falcatum L. on the healing of gastric ulcer induced by acetic acid in rats. Phytother Res. 2002;16(1):91-93. https://doi.org/10.1002/ptr.986
  17. Chang WC, Hsu FL. Inhibition of platelet activation and endothelial cell injury by flavan-3-ol and saikosaponin compounds. Prostaglandins, leukotrienes, and essential fatty acids. 1991;44(1):51-56. https://doi.org/10.1016/0952-3278(91)90144-T
  18. Nose M, Amagaya S, Ogihara Y. Corticosterone secretion-inducing activity of saikosaponin metabolites formed in the alimentary tract. Chemical & pharmaceutical bulletin. 1989;37(10): 2736-2740. https://doi.org/10.1248/cpb.37.2736
  19. Abe H, Sakaguchi M, Odashima S, Arichi S. Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat. Naunyn-Schmiedeberg's archives of pharmacology. 1982;320(3):266-271. https://doi.org/10.1007/BF00510139
  20. Niikawa M, Sakai Y, Ose Y, Sato T, Nagase H, Kito H, Sato M, Mizuno M. Enhancement of the mutagenicity of Trp-P-1, Trp-P-2 and benzo[a]pyrene by bupleuri radix extract. Chemical & pharmaceutical bulletin. 1990;38(7): 2035-2039. https://doi.org/10.1248/cpb.38.2035
  21. Organization for Economic Co-Operation and Development (Ed.) 474.(1997) OECD Guideline for the Testing of Chemicals, No. 474: Mammalian Erythrocyte Micronucleus Test.
  22. Irwin S. Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse. Psychopharmacologia. 1968;13(3): 222-257. https://doi.org/10.1007/BF00401402
  23. Dourish CT. Effects of drugs on spontaneous motor activity. Greenshaw AJ, Dourish CT, editors. Clifton: Humana Press; 1987. 325-334 p.
  24. Schmid W. The micronucleus test. Mutat Res. 1975;31(1):9-15. https://doi.org/10.1016/0165-1161(75)90058-8
  25. Heddle JA, Stuart E, Salamone MF. The bone marrow micronucleus test. In: Kilbey BJ, Legator M, Nichols W, Ramel C, editors. Handbook of mutagenicity test procedures. Amsterdam: Elsevier; 1984. p. 441-457.
  26. Levene A. Pathological factors influencing excision of tumours in the head and neck. Part I. Clinical otolaryngology and allied sciences. 1981;6(2):145-151. https://doi.org/10.1111/j.1365-2273.1981.tb01800.x
  27. Ludbrook J. Update: microcomputer statistics packages. A personal view. Clinical and experimental pharmacology & physiology. 1997;24(3-4):294-296. https://doi.org/10.1111/j.1440-1681.1997.tb01823.x
  28. Matter B, Schmid W. Trenimon-induced chromosomal damage in bone-marrow cells of six mammalian species, evaluated by the micronucleus test. Mutat Res. 1971;12(4): 417-425. https://doi.org/10.1016/0027-5107(71)90092-3
  29. Heddle JA. A rapid in vivo test for chromosomal damage. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. 1973;18(2):187-190. https://doi.org/10.1016/0027-5107(73)90035-3
  30. von Ledebur M, Schmid W. The micronucleus test. Methodological aspects. Mutat Res. 1973;19(1):109-117. https://doi.org/10.1016/0027-5107(73)90118-8
  31. Heddle JA, Hite M, Kirkhart B, Mavournin K, MacGregor JT, Newell GW, Salamone MF. The induction of micronuclei as a measure of genotoxicity: a report of the US Environmental Protection Agency Gene-Tox Program. Mutation Research/Reviews in Genetic Toxicology. 1983;123(1):61-118. https://doi.org/10.1016/0165-1110(83)90047-7
  32. Ashby J. Is there a continuing role for the intraperitoneal injection route of exposure in short-term rodent genotoxicity assays? Mutation research. 1985;156(3):239. https://doi.org/10.1016/0165-1218(85)90069-2
  33. Grochow L, Perry M. Covalent DNA-binding drugs. In: Perry M, editor. The Chemotherapy Source Book. Baltimore: Williams & Wilkins; 1997. p. 293-316.
  34. Miyauchi A, Hiramine C, Tanaka S, Hojo K. Differential effects of a single dose of cyclophosphamide on T cell subsets of the thymus and spleen in mice: flow cytofluorometry analysis. The Tohoku journal of experimental medicine. 1990;162(2):147-167. https://doi.org/10.1620/tjem.162.147
  35. El-Bayoumy K. The protective role of selenium on genetic damage and on cancer. Mutat Res. 2001;475(1-2):123-139. https://doi.org/10.1016/S0027-5107(01)00075-6