Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지
DOI QR코드

DOI QR Code

A 90-Day Repeated Oral Dose Toxicity Study of Alismatis Rhizoma Aqueous Extract in Rats

  • Lee, Mu-Jin (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Jung, Ho-Kyung (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Lee, Ki-Ho (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Jang, Ji-Hun (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Sim, Mi-Ok (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Seong, Tea-Gyeong (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Ahn, Byung-Kwan (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Shon, Jin-Han (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Ham, Seong-Ho (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Cho, Hyun-Woo (Division of Tradition Korean Medicine Research, National Development Institute of Korean Medicine) ;
  • Kim, Yong-Min (Preclinical Research Center, MEDVILL Co.) ;
  • Park, Sung-Jin (Preclinical Research Center, MEDVILL Co.) ;
  • Yoon, Ji-Young (Jeonju AgroBio-Materials Institute) ;
  • Ko, Je-Won (College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University) ;
  • Kim, Jong-Choon (College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University)
  • Received : 2018.08.22
  • Accepted : 2018.11.06
  • Published : 2019.04.15
Download PDF
⟨ Previous Next ⟩

Abstract

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

Keywords

References

  1. Choi, Y.J., Yoon, Y.J., Choi, H.S., Park, S.R., Oh, S.H., Jeong, S.M., Suh, H.R. and Lee B.H. (2011) Effects of medicinal herb extracts and their components on steatogenic hepatotoxicity in Sk-hep1 cells. Toxicol. Res., 27, 122-216.
  2. Lee, J.C., Lee, E. and Lee, Y.C. (2008) Effects of Rhizoma Alismatis on lipid composition and TBARS concentration in rat fed high fat diet. Kor. J. Herbol., 23, 113-117.
  3. Kim, S.E., Rhyu, D.Y., Yokozawa, T. and Park, J.C. (2007) Antioxidant effect of Alisma plantago-aquaticavar. orientale and its main component. Kor. J. Pharmacogn., 38, 372-375.
  4. National Institute of Medicinal Materials (2004) Medicinal Plants and Animals, Science and Technology. National Institute of Medicinal Materials, Hanoi.
  5. Tian, T., Chen, H. and Zhao, Y.Y. (2014) Traditional uses, phytochemistry, pharmacology, toxicology and quality control of Alisma orientale (Sam.) Juzep: a review. J. Ethnopharmacol., 158, 373-387. https://doi.org/10.1016/j.jep.2014.10.061
  6. Lee, S.I. (1981) Studies on the diuretic action of Oryeongsan and Kami-Oryengsan. Kor. J. Pharmacogn, 12, 31-43.
  7. Ahn, M.J., Lee, C.H., Shin,Y.W., Chun, M.S., Kim, C.Y. and Kim, J. (2008) Determination of alisol B 23-acetate and alisol C 23-acetate in Alismatis rhizoma by HPLC-ESI-MS. Nat. Prod. Sci., 14, 152-155.
  8. Huang, D.S. and Shin, H.K. (2009) A study on compositions and dosages of Yukmijihwang-Hwan by literature review on the classics of oriental medicine. Kor. J. Orient. Med. Prescr., 17, 17-28.
  9. Yu, D.J., Yoon, K.M., Jang, S.Y., Lee, Y.K. and Kang, S.B. (2009) Nephroprotective effects of Taeksa-San aqueous extracts on cisplatin-induced rat acute renal failure. Kor. J. Orient. Int. Med., 30, 832-844.
  10. Mi, Q.W., Cao, Z.G., Liu, J.H., Wu, J.Z., Yin, C.P., Zhou, S.W. and Ye, Z.Q. (2005) Effects of active fraction of Alisma orientale on osteopontin expression in renal tissue of urolithiasis model rat with calcium oxalate stone. Chin. Tradit. Herbal Drugs, 36, 1827-1830. https://doi.org/10.3321/j.issn:0253-2670.2005.12.029
  11. Jiang, Z.Y., Zhang, X.M., Zhang, F.X., Liu, N., Zhao, F., Zhou, J. and Chen, J.J. (2006) A new triterpene and antihepatitis B virus active compounds from Alisma orientalis. Planta Med., 72, 951-954. https://doi.org/10.1055/s-2006-947178
  12. Zhao, M., Chen, J.Y., Xu, L.J., Goedecke, T., Zhang, X.Q., Duan, J.A. and Che, C.T. (2012) Cis-aconitic anhydride ethyl ester and phenolic compounds from the seeds of Alisma orientale. Nat. Prod. Commun., 7, 785-787.
  13. Tomoda, M., Gonda, R., Shimizu, N. and Ohara, N. (1994) Characterization of an acidic polysaccharide having immunological activities from the tuber of Alisma orientale. Biol. Pharm. Bull., 17, 572-576. https://doi.org/10.1248/bpb.17.572
  14. Wang, L.X.,Wu, Q.N., Zhang, Q., Peng, G.P. and Ding, A.W. (2008) Basic study of diuretic active compounds in Rhizoma Alismatis. West China J. Pharm. Sci., 23, 670-672. https://doi.org/10.3969/j.issn.1006-0103.2008.06.017
  15. Duan, X.Y., Wang, J.B., Yin, X.L., Yan, S.F. and Xiao, Y. (2004) A 60-day feeding study of Rhizoma Alismatis Orientalis in SD rats. Chin. J. Food Hyg., 16, 108-111. https://doi.org/10.3969/j.issn.1004-8456.2004.02.003
  16. Zhu, J.H., Bao, X.R., He, H.P. and Zhang, Q. (2007) Experimental studies of nephrotoxicity induced by Alisma orientalis in rats. Pharmacol. Clin. Chin. Mater. Med., 23, 60-62.
  17. Huang, M.Q., Xu, W., Wu, S.S., Lu, J.J. and Chen, X.P. (2013) A 90-day subchronic oral toxicity study of triterpeneenriched extract from Alismatis rhizoma in rats. Food Chem. Toxicol., 58, 318-323. https://doi.org/10.1016/j.fct.2013.05.009
  18. Seok, J.H., Roh, H.S., Jeong, J.Y. and Ha, H.Y. (2013) Acute oral toxicity of Alismatis rhizoma in SD rats. J. Kor. Med. Ophthalmol. Otolaryngol. Dermatol., 26, 15-25. https://doi.org/10.6114/jkood.2013.26.4.015
  19. Roh, H.S., Seok, J.H., Jeong, J.Y., Lee, J.K., Kim, T.S., Choi, H.K. and Ha, H.Y. (2014) Repeated dose oral toxicity study of Alismatis rhizoma in SD rats. J. Kor. Med. Ophthalmol. Otolaryngol. Dermatol., 27, 79-90. https://doi.org/10.6114/jkood.2014.27.1.079
  20. Chang, H.M. and But, P.P.H. (1987) Pharmacology and Applications of Chinese Materia Medica (vol. II), World Scientific Publishing Co., Singapore, pp. 802-805.
  21. Kreituss, I. (2016) Kinetic resolution of cyclic secondary amines and synthesis of partially saturated N-heterocycles. Swiss Federal Institute of Technology (ETH Zurich), ETH 23440.
  22. Buyev, E.M., Moshkin, V.S. and Sosnovsky, V.Ya. (2017) (3+2) Cycloaddition of N-methylazomethinylide, obtained from sarcosine and formaldehyde, to enones and enamides with CH-and NH-acidity. Chem. Heterocycl. Compd., 53, 167-172. https://doi.org/10.1007/s10593-017-2035-7
  23. Muller, C. (2006) Studies on Olefin Metathesis and Its Application in the Synthesis of Middle Rings. Department of Chemistry, University of Dortmund.
  24. Dai, Q., Jiang, Y., Yu, J.T. and Cheng, J. (2015) Palladiumcatalyzed three-component reaction of N-tosyl hydrazones, isonitriles and amines leading to amidines. Chem. Commun., 51, 16645. https://doi.org/10.1039/C5CC06771E
  25. Makabel, B., Zhao, Y., Wang, B., Bai, Y., Zhang, Q., Wu, L. and Lv, Y. (2008) Stability and structure studies on alisol A 24-acetate. Chem. Pharm. Bull., 56, 41-45. https://doi.org/10.1248/cpb.56.41
  26. Lee, J.H., Kwon, O.S., Jin, H.G., Woo, E.R., Kim, Y.S. and Kim, H.P. (2012) The Rhizomes of Alisma orientale and alisol derivatives inhibit allergic response and experimental atopic dermatitis. Biol. Pharm. Bull., 35, 1581-1587. https://doi.org/10.1248/bpb.b110689
  27. Morris, M. (1982) Neurohypophyseal response to dehydration in the spontaneously hypertensive rat. Hypertension, 4, 161-166. https://doi.org/10.1161/01.HYP.4.1.161
  28. Ogawa, Y., Aoki, K., Kato, J. and Iwasaki, K.I. (2013) Differential effects of mild central hypovolemia with furosemide administration vs. lower body suction on dynamic cerebral autoregulation. J. Appl. Physiol., 114, 211-216. https://doi.org/10.1152/japplphysiol.00741.2012
  29. Feng, Y.L., Chen, H., Tian, T., Chen, D.Q., Zhao, Y.Y. and Lin, R.C. (2014) Diuretic and antidiuretic activities of the ethanol and aqueous extracts of Alismatis rhizoma. J. Ethnopharmacol., 154, 386-390. https://doi.org/10.1016/j.jep.2014.04.017
  30. Petterino, C. and Argentino-Storino, A. (2006) Clinical chemistry and haematology historical data in control Sprague-Dawley rats from pre-clinical toxicity studies. Exp. Toxicol. Pathol., 57, 213-219. https://doi.org/10.1016/j.etp.2005.10.002
  31. Han, Z.Z., Xu, H.D., Kim, K.H., Ahn, T.H., Bae, J.S., Lee, J.Y., Gil, K.H., Lee, J.Y., Woo, S.J., Yoo, H.J., Lee, H.K., Kim, K.H., Park, C.K., Zhang, H.S. and Song, S.W. (2010) Reference data of the main physiological parameters in control Sprague-Dawley rats from pre-clinical toxicity studies. Lab. Anim. Res., 26, 153-164. https://doi.org/10.5625/lar.2010.26.2.153
  32. Lee, J.M., Lee, M.A., Do, H.N., Song, Y.I., Bae, R.J.N., Lee, H.Y., Park, S.H., Kang, J.S. and Kang, J.K. (2012) Historical control data from 13-week repeated toxicity studies in Crj: CD (SD) rats. Lab. Anim. Res., 28, 115-121. https://doi.org/10.5625/lar.2012.28.2.115
  33. Hard, G.C. and Khan, K.N. (2004) A contemporary overview of chronic progressive nephropathy in the laboratory rat, and its significance for human risk assessment. Toxicol. Pathol., 32, 171-180. https://doi.org/10.1080/01926230490422574
  34. Wolf, D.C. and Mann, P.C. (2005) Confounders in interpreting pathology for safety and risk assessment. Toxicol. Appl. Pharmacol., 202, 302-308. https://doi.org/10.1016/j.taap.2004.06.022
  35. Hard, G.C., Johnson, K.J. and Cohen, S.M. (2009) A comparison of rat chronic progressive nephropathy with human renal disease-implications for human risk assessment. Crit. Rev. Toxicol., 39, 332-346. https://doi.org/10.1080/10408440802368642
  36. Lee, M.Y., Seo, C.S., Kim, J.Y. and Shin, H.K. (2015) Genotoxicity evaluation of Oryeong-san water extract using in vitro and in vivo tests. BMC Complement. Altern. Med., 15,