Advertisement

Neuraminidase Inhibitors fromReynoutria elliptica

  • Chu-Hyun Lee
  • Sang-ln Kim
  • Kyung-Bok Lee
  • Yung-Choon Yoo
  • Si-Young Ryu
  • Kyung-Sik Song
Research Articles Articles

Abstract

In the course of screening neuraminidase inhibitors from herbal medicines, Reynoutria elliptica exhibited high inhibitory activity. Four active compounds were isolated from the ethyl acetate soluble fraction by consecutive purification using sillica gel, Sephadex LH-20 chromatography, and recrystallization. The chemical structures of these compounds were identified as 1,3,8-trihy-droxy-6-methylanthraquinone (emodin) 1,8-dihydroxy-3-methoxy-6-methylanthraquinone (emodin 3-methyl ether; physcion), 1,3,8-trihydroxy-6-hydoxymethylanthraquinone (ω-hydroxyemodin), and 3,5,4′-trihydroxystilbene (trans-resvertrol) by spectral data including MS,1 H-, and13 C-NMR. The IC50 values of emodin, emodin 3-methyl ether, ω-hydroxyemodin, andtrans-resvertrol were 2.81, 74.07, 10.49, and 8.77 μM, respectively. They did not inhibit other glycosidase such as glucosidase, mannosidase, and galactosidase, indicating that they were relatively specific inhibitors of neuraminidase.

Key words

Neuraminidase inhibitor Influenza Emodin Emodin 3-methyl ether Physcion ω-Hydroxy emodin trans-Resveratrol Reynoutria elliptica 

References

  1. Burmeister, W. P., Ruigrok, R. W., and Cusack, S., The 2.2 resolution crystal structure of influenza B neuraminidase and its complex with sialic acid.EMBO J., 11, 49–56 (1992).PubMedGoogle Scholar
  2. Chen, L., Han, Y., Yang, F., and Zhang, T., High-speed counter-current chromatography separation and purification resver-trol and piceidPolygonum cuspidatum.J. Chromatogr A., 907, 343–346 (2001).PubMedCrossRefGoogle Scholar
  3. Colman, P. M., Influenza virus neuraminidase: structure, antibiotics and inhibitors.Protein Sci., 3, 1687–1696 (1994).PubMedCrossRefGoogle Scholar
  4. Colman, P. M., Design and antiviral properties of influenza virus neuraminidase inhibitors.Pure Appl. Chem., 67, 1683–1688 (1995).CrossRefGoogle Scholar
  5. Colman, P. M., A novel approach to antiviral to therapy for influenza.J. Antimicrob. Chemother, 44, 17–22 (1999).PubMedCrossRefGoogle Scholar
  6. Francis, G. W., Aksnes, D. W., and Holt, Q., Assignment of the1H and13C NMR spectra of anthraquinone glycoside fromRhamnus frangula.Mag. Res. Chem., 36, 769–772 (1998).CrossRefGoogle Scholar
  7. Gottschalk, A., The specific enzyme of influenza virus andVibrio cholerae.Biochem. Biophys. Acta., 23, 645–646 (1957).PubMedCrossRefGoogle Scholar
  8. Klenk, H. O. and Rott, R., The molecular biology of influenza virus pathogenicity.Adv. Virus Res., 34, 247–280 (1988).PubMedCrossRefGoogle Scholar
  9. Ko, S. K., Whang, W. K., and Kim, I. H., Anthraquinone and stilbene derivatives from the cultivated Korean Rhubarb Rhizomes.Arch. Pharm. Res., 18, 282–288 (1995).CrossRefGoogle Scholar
  10. Lin, C., Eichelberger, M. C., Compans, R. W., and Air, G. M., Influenza type A virus neuraminidase does not play a role in viral entry, replication, assembly or budding.J. Virol., 69, 1099–1106 (1995).Google Scholar
  11. Likhitwitayawuid, K., Sritularak, B., and De-Eknamkul, W., Tyrosinase inhibitors fromArtocarpus gomezianus.Planta Medica, 66, 275–277 (2000).PubMedCrossRefGoogle Scholar
  12. Murakami, H., Kobayashi, J., Musuda, T., Morooka, N., and Ueno, Y., ω-Hydroxyemodin, a major hepatic metabolite of emodin in various animals and its mutagenic activity.Mutation Res., 180, 147–153 (1987).PubMedGoogle Scholar
  13. Myers, R. W., Lee, R. T., Lee, Y. C., and Thomas, G. H., The synthesis of 4-methylumberiferyl α-ketoside ofN-acetyl-neuraminic acid and its use in a fluorometric assay for neuraminidase.Anal. Biochem., 101, 166–174 (1980).PubMedCrossRefGoogle Scholar
  14. Palese, P. and Compans, R. W., Inhibition of influenza virus replication in tissue culture by 2-deoxy-2, 3-dehydro-N-trifluoroacetyl neuraminic acid (FANA): mechanism of action.J. General Virol., 33, 159–163 (1976).CrossRefGoogle Scholar
  15. Palese, P., Tabita, U., Ueda, M., and Compans, R. W., Characterization of temperature sensitive influenza virus mutants.Virology, 61, 397–410 (1974).PubMedCrossRefGoogle Scholar
  16. Varghee, J. N., Mckimm-Breschkin, J. L., Caldwell, J. B., Kortt, A. A., and Colman, P. M., The structure of the complex between influenza virus neuraminidase and sialic acid, the viral receptor.Protein, 14, 327–332 (1992).CrossRefGoogle Scholar
  17. von Itzstein, N., Kok, G. B., and Pegg, M. S., Rational design of potent sialidase-based inhibitors of influenza virus replication.Nature, 363, 418–423 (1993).CrossRefGoogle Scholar
  18. Willey, D. C. and Skehel, J. J., The structure and function of the hemagglutinin membrane glycoprotein of influenza virus.Annu. Rev. Biochem., 56, 365–394 (1987).CrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2003

Authors and Affiliations

  • Chu-Hyun Lee
    • 1
  • Sang-ln Kim
    • 1
  • Kyung-Bok Lee
    • 2
  • Yung-Choon Yoo
    • 2
  • Si-Young Ryu
    • 3
  • Kyung-Sik Song
    • 1
  1. 1.Division of Applied Biology & Chemistry, College of Agriculture & Life SciencesKyungpook National UniversitySankyuk-DongKorea
  2. 2.College of MedicineKonyang UniversityNonsan, ChoongnamKorea
  3. 3.Korea Research Institute of Chemical TechnologyDaejonYusung-GuKorea

Personalised recommendations