YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Study on Mutagenicity of DehydroevodiamineㆍHCl(DHED)

치료제 DehydroevodiamineㆍHCl(DHED)의 변이원성 연구

  • Published : 2002.06.01
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Abstract

Dehydroevodiamine HCl (DHED), which is a component separated from Evodia rutaecarpa Bentham, has novel anticholinesterase and antiamnesic activities in the scopolamine-induced amnesia model. Several studies suggest that DHED might be an effective drug for the Alzheimer's disease and the vascular type of dementia. In order to evaluate the mutagenic potential of DHED, Salmonella typhimurium reversion assay, chromosomal aberration test on Chinese hamster lung cells, in vivo micronucleus assay using mouse bone marrow cells, and comet assay were performed. DHED did not increase the number of revertant in the reverse mutation test using Salmonella typhimurium TA1535, TA1537, TA98, TA100. DHED HCl, at concentration of 5 and 10 $\mu\textrm{g}$/mι, increased the number of chromosome aberrated Chinese hamster lung cells with 5 and 10％, respectively. In mouse micronucleus test, no significant increase in the occurrence of micronucleated polychromatic erythrocyte was observed in ICR mice orally administered with DHED. DHED was tested for ability to induce genotoxic effect in L5178Y cells (mouse lymphoma cells) using the single cell gel electrophoresis assay (comet assay). In comet assay, tail moment did not increase in L5178Y cells treated with 10, 100, 300 $\mu$M DHED.

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References

  1. Whitehouse P. J., Price D. L., Struble R. G., Clark R. W., Coyle J. T., and DeLong M. R. : Alzheimer's disease and senile dementia:loss of neurons in the basal forebrain. Science. 215, 1237 (1982)
  2. Marx J. L. : Alzheimer's drug trial put on hold. Science. 238, 1041 (1987) https://doi.org/10.1126/science.3317822
  3. Rogers R. L., Meyer J. S., Mortel K. F., Mahurin R. K., and Judd B.W.: Decreased cerebral blood flowpreceds multi-infact dementia, but follows senile dementia of Alzheimer type. Neurology. 36, 1 (1986)
  4. Ni J. W., Ohta H., Matsumoto K., and Watanabe H. : Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res. 653, 231 (1994) https://doi.org/10.1016/0006-8993(94)90394-8
  5. Yonemori F., Yamada H., Yamaguchi T., Uemura A. and Tamura A. : Spatial memory disturbance after focal cerebral ischemia in rats. J. Cereb, Blood Flow Metab. 16, 973 (1996)
  6. Yang H. Y., Li S. Y. and Chen C. F. : Hypotensive effects of dehydroevodiamine,a quinazolinocarboline alkaloid isolated from Evodia rutaecarpa. Asia Pac. J. Pharmacol. 3, 191 (1998)
  7. Haji A., Momose Y., Takeda R., Nakanishi S., Horiuchi T., and Arisawa M. : Increased feline cerebral blood flow induced by dehydroevodiamine hydrochloride from Evodia rutaecarpa. J. Nat. Prod. 57, 387 (1994) https://doi.org/10.1021/np50105a009
  8. Loh S. H., Lee A. R., Huang W. H., and Lin C. I. : Ionic mechanisms responsible for the antiarrhythmic action of dehydroevodiamine in guinea-pig isloated cardiomyocytes. Br. J. Pharmacol. 106, 517 (1992)
  9. Maron,. D. M. and Ames, B. M. : Revised methods for the Salmonella mutagenicity test. Mutat. Res., 113, 173 (1983)
  10. Dean, B. J. and Danford, N. : Assays for the detection of chemically induced chromosome damage in cultured mammalian cells. In Mutagenicity testing, Venitt, S. and Parry, J. M. (eds.), IRL Press, Oxford, pp. 187-232 (1983)
  11. Singh, N. P., McCoy, M. T., Tice, R. R., Schneider, E. L. : A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell. Res., 175, 184 (1988)