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Subchronic Oral Toxicity Study of Acanthopanax divaricatus var. albeofructus in Rats

  • Kim, Myoung Jun (Department of Pathology, Biotoxtech Co., Ltd.) ;
  • Lee, Mi Ju (Department of Pathology, Chronic Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency) ;
  • Lee, Yong-Hoon (Department of Pathology, Chronic Inhalation Toxicity Research Center, Chemicals Toxicity Research Bureau, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency) ;
  • Park, Sun Hee (Department of Pathology, Biotoxtech Co., Ltd.) ;
  • Kim, Duyeol (Department of Pathology, Biotoxtech Co., Ltd.) ;
  • Park, Cheol Beom (Department of Pathology, Biotoxtech Co., Ltd.) ;
  • Kang, Jin Seok (Department of Biomedical Laboratory Science, Namseoul University) ;
  • Kang, Jong-Koo (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Chungbuk National University)
  • Received : 2016.06.30
  • Accepted : 2016.12.09
  • Published : 2017.01.15

Abstract

Acanthopanax divaricatus (Siebold & Zucc.) Seem. var. albeofructus (ADA), a traditional medical herb, has been used to treat arthritis and muscular injury, to strengthen muscle and bone, and to get vital energy. However, information regarding its toxicity is limited. ADA was administered by oral gavage to groups of rats at doses of 0 (control), 1,000, 1,500, 2,000, 2,500, and 3,000 mg/kg five times per week for 13 weeks. Mortality, clinical signs, body weights, food consumption, hematology, serum chemistry, urinalysis, organ weights, necropsy, histopathological finding, vaginal cytology, and sperm morphology were compared between control and ADA-treated groups. Salivation was intermittently observed in both sexes receiving 2,500 and 3,000 mg/kg directly after dosing. Absolute liver weights increased in females receiving 2,000, 2,500, and 3,000 mg/kg ADA (P < 0.05, P < 0.01, and P < 0.01, respectively) and so did the relative liver weights (P < 0.001). Salivation and increased liver weight were ADA-related changes but not considered to be adverse effects. Salivation was intermittent and transient, and the liver weight increase was minor and not accompanied by other changes such as hepatic morphological or functional alterations. The no-observed-adverse-effect-level was determined to be at least 3,000 mg/kg in both sexes of rats.

Keywords

References

  1. Yook, C.S., Rho, Y.S., Seo, S.H., Leem, J.Y. and Han, D.R. (1996) Chemical components of Acanthopanax divaricatus and anticancer effect in leaves. Yakhakhoe Chi, 40, 251-261.
  2. Kim, J.-H. and Hahn, D.-R. (1981) Studies on the chemical constituents of Acanthopanax chiisanensis Nakai roots. Arch. Pharm. Res., 4, 59-62. https://doi.org/10.1007/BF02856442
  3. Takasugi, N., Moriguchi, T., Fuwa, T., Sanada, S., Ida, Y., Shoji, J. and Saito, H. (1985) Effect of Eleutherococcus senticosus and its components on rectal temperature, body and grip tones, motor coordination, and exploratory and spontaneous movements in acute stressed mice. Shoyakugaku Zasshi, 39, 232-237.
  4. Foster, S. and Chongxi, Y. (1992) Herbal emissaries: bringing Chinese herbs to the West: a guide to gardening, herbal wisdom, and well-being, Healing arts press, Rochester, Vermont.
  5. Yamazaki, T., Matsumura, T., Tsukiyama, T. and Tokiwa, T. (2006) Anti-inflammatory effects of eleutheroside E from Acanthopanax senticosus. Tissue Cult. Res. Commun. 25, 137-145.
  6. Lee, D., Park, J., Yoon, J., Kim, M.Y., Choi, H.Y. and Kim, H. (2012) Neuroprotective effects of Eleutherococcus senticosus bark on transient global cerebral ischemia in rats. J. Ethnopharmacol., 139, 6-11. https://doi.org/10.1016/j.jep.2011.05.024
  7. Huang, L.Z., Wei, L., Zhao, H.F., Huang, B.K., Rahman, K. and Qin, L.P. (2011) The effect of Eleutheroside E on behavioral alterations in murine sleep deprivation stress model. Eur. J. Pharmacol., 658, 150-155. https://doi.org/10.1016/j.ejphar.2011.02.036
  8. Nishibe, S., Kinoshita, H., Takeda, H. and Okano, G. (1990) Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. Chem. Pharm. Bull., 38, 1763-1765. https://doi.org/10.1248/cpb.38.1763
  9. Hong, S.S., Hwang, J.S., Lee, S.A., Hwang, B.Y., Ha, K.W., Ze, K.R., Seung, R.S., Ro, J.S. and Lee, K.S. (2001) Isolation and quantitative analysis of acanthoside D from Acanthopanacis cortex. Saengyak Hakhoechi, 32, 316-321.
  10. Kang, J.S., Linh, P.T., Cai, X.F., Kim, H.S., Lee, J.J. and Kim, Y.H. (2001) Quantitative determination of eleutheroside B and E from Acanthopanax species by high performance liquid chromatography. Arch. Pharmacol. Res., 24, 407-411. https://doi.org/10.1007/BF02975184
  11. Bae, E.A., Yook, C.S., Oh, O.J., Chang, S.Y., Nohara, T. and Kim, D.H. (2001) Metabolism of chiisanoside from Acanthopanax divaricatus var. albeofructus by human intestinal bacteria and its relation to some biological activities. Biol. Pharm. Bull., 24, 582-585. https://doi.org/10.1248/bpb.24.582
  12. Oh, O.J., Chang, S.Y., Yook, C.S., Yang, K.S., Park, S.Y. and Nohara, T. (2000) Two 3,4-seco-lupane triterpenes from leaves of Acanthopanax divaricatus var. albeofructus. Chem. Pharm. Bull., 48, 879-881. https://doi.org/10.1248/cpb.48.879
  13. Lim, E.J., Do, G.M., Shin, J.H. and Kwon, O. (2013) Protective effects of Acanthopanax divaricatus vat. albeofructus and its active compound on ischemia-reperfusion injury of rat liver. Biochem. Biophys. Res. Commun., 432, 599-605. https://doi.org/10.1016/j.bbrc.2013.02.039
  14. Jung, H.J., Nam, J.H., Choi, J., Lee, K.T. and Park, H.J. (2005) Antiinflammatory effects of chiisanoside and chiisanogenin obtained from the leaves of Acanthopanax chiisanensis in the carrageenan- and Freund's complete adjuvant-induced rats. J. Ethnopharmacol., 97, 359-367. https://doi.org/10.1016/j.jep.2004.11.026
  15. Lee, S., Shin, D.S., Oh, K.B. and Shin, K.H. (2003) Antibacterial compounds from the leaves of Acanthopanax senticosus. Arch. Pharmacol. Res., 26, 40-42. https://doi.org/10.1007/BF03179929
  16. Kim, Y.-O., Cho, D.-H., Chung, H.-J., Kim, J.-H., Chang, S.-Y., Yook, C.-S., Yang, K.-S. and Oh, O.-J. (1999) Effects of lupane-triterpenoids on mitogen-induced proliferation of lymphocytes. Yakhak Hoechi, 43, 208-213.
  17. Won, J.H., Park, S.Y., Nam, S.G., Park, H.J., Choi, J.W. and Lee, K.T. (2005) Inhibition of lipopolysaccharide-induced expression of inducible nitric oxide and cyclooxygenase-2 by chiisanoside via suppression of nuclear factor-kappaB activation in RAW 264.7 macrophage cells. Biol. Pharm. Bull., 28, 1919-1924. https://doi.org/10.1248/bpb.28.1919
  18. Ko, R.J. (2004) A U.S. perspective on the adverse reactions from traditional Chinese medicines. J. Chin. Med. Assoc., 67, 109-116.
  19. Xiang, B., Peng, Y. and Jiang, Y.-G. (2013) A report on the analysis of 365 cases of adverse reactions of Chinese patent drugs for heart cerebrovascular diseases. Afr. J. Pharm. Pharmacol., 7, 1267-1271. https://doi.org/10.5897/AJPP12.147
  20. Hong, C.E., Cho, M.C., Jang, H.A. and Lyu, S.Y. (2011) Mutagenicity and anti-mutagenicity of Acanthopanax divaricatus var. albeofructus. J. Toxicol. Sci., 36, 661-668. https://doi.org/10.2131/jts.36.661
  21. Sun, Y.N., Li, W., Song, S.B., Yan, X.T., Yang, S.Y. and Kim, Y.H. (2014) NF-${\kappa}B$ Inhibitory Activities of Phenolic and Lignan Components from the Stems of Acanthopanax divaricatus var. albeofructus. Nat. Prod. Sci., 20, 232-236.
  22. Matsuo, R., Yamauchi, Y., Kobashi, M., Funahashi, M., Mitoh, Y. and Adachi, A. (2001) Role of parabrachial nucleus in submandibular salivary secretion induced by bitter taste stimulation in rats. Auton. Neurosci., 88, 61-73. https://doi.org/10.1016/S1566-0702(01)00234-X
  23. Cunningham, J.G. and Klein, B.G. (2007) Textbook of Veterinary Physiology (4th edition), Saunders, St. Louis, Missouri.
  24. Haschek, W.M., Rousseaux, C.G., Walling, M.A., Bolon, B., Ochoa, R. and Mahler, B.W. (2013) Haschek and Rousseaux's Handbook of Toxicologic Pathology (3rd edition), Academic Press, London.
  25. Karbe, E., Williams, G.M., Lewis, R.W., Kimber, I. and Foster, P.M.D. (2001) Distinguishing between adverse and nonadverse effects. J. Toxicol. Pathol., 14, 321-325. https://doi.org/10.1293/tox.14.321
  26. Hall, A.P., Elcombe, C.R., Foster, J.R., Harada, T., Kaufmann, W., Knippel, A., Kuttler, K., Malarkey, D.E., Maronpot, R.R., Nishikawa, A., Nolte, T., Schulte, A., Strauss, V. and York, M.J. (2012) Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes--conclusions from the 3rd International ESTP Expert Workshop. Toxicol. Pathol., 40, 971-994. https://doi.org/10.1177/0192623312448935
  27. Amacher, D.E., Schomaker, S.J. and Burkhardt, J.E. (1998) The relationship among microsomal enzyme induction, liver weight and histological change in rat toxicology studies. Food Chem. Toxicol., 36, 831-839. https://doi.org/10.1016/S0278-6915(98)00066-0
  28. Kasai, R., Matsumoto, K., Taniyasu, S., Tanaka, O., Kim, J.-H. and Hahn, D.-R. (1986) 3,4-Seco-lupane type triterpene glycosyl esters from a Korean medicinal plant, Acanthopanax chiisanensis (Araliaceae). Chem. Pharm. Bull., 34, 3284-3289. https://doi.org/10.1248/cpb.34.3284
  29. Okamura, T., Suzuki, S., Ogawa, T., Kobayashi, J., Kusuoka, O., Hatayama, K., Mochizuki, M., Hoshiya, T., Okazaki, S. and Tamura, K. (2011) Background data for general toxicology parameters in RccHan:WIST rats at 8, 10, 19 and 32 weeks of age. J. Toxicol. Pathol., 24, 195-205. https://doi.org/10.1293/tox.24.195