Zeitschrift für Phytotherapie 2008; 29(2): 65-70
DOI: 10.1055/s-2008-1077269
Forschung

© Sonntag Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG

Wirkung von Pflanzenextrakten auf die Neuraminidase-Aktivität

Sverre Morten Schwerdtfeger, Matthias F. Melzig
Further Information

Publication History

Publication Date:
18 June 2008 (online)

Zusammenfassung

Die Volksmedizin bietet bei der Suche nach neuen Substanzen gegen Influenzaviren einen wichtigen Anknüpfungspunkt, da hier Pflanzen seit mehreren hundert Jahren bei Grippe oder grippalen Infekten Anwendung finden, ohne dass sie jedoch validiert oder ihre Wirkmechanismen untersucht worden sind. Verschiedene pflanzliche Extrakte wurden daher mittels eines Enzymtests in vitro auf ihre Fähigkeit hin untersucht, die Neuraminidase zu inhibieren. Zanamivir (IC50 = 215 µM) diente als Referenzinhibitor. Die methanolischen Extrakte von Geranium sanguineum (IC50 = 3,9 × 10-4 mg/ml), Eucalyptus globulus (IC50 = 1,50 × 10-3 mg/ml), Ginkgo biloba (IC50 = 2,31 × 10-3 mg/ml) und der ethanolische Extrakt von Bergenia ligulata (IC50 = 3,20 × 10-3 mg/ml) hemmten die Neuraminidase stark. Schwache Hemmeffekte erzielten dagegen u.a. die Extrakte von Echinacea angustifolia, Eleuterococcus senticosus und Zingiber officinale. Naturstoffe und pflanzliche Extrakte könnten eine vielversprechende Quelle bei der Suche nach Neuraminidase-Inhibitoren sein.

Summary

Effects of plant extracts on neuraminidase activity

The seasonal flu epidemics are caused by Influenza A and B viruses. In 2002, EU regulatory approval was granted for the neuraminidase inhibitors (NAI) Zanamivir and Oseltamivir. Due to its long tradition over several hundred years, ethnomedicine provides a promising source for new drugs against flu and colds. Previously, neither the validity nor the efficacy mechanisms of the drugs were wholly investigated. Therefore different extracts of plants used in traditional medicine were tested in an in vitro enzyme assay for their ability to inhibit prokaryotic neuraminidase. Zanamivir served as reference inhibitor (IC50 = 215 µM). The methanolic extract of Geranium sanguineum (IC50 = 3.9 × 10-4 mg/ml), Eucalyptus globulus (IC50 = 1.50 × 10-3 mg/ml), Ginkgo biloba (IC50 = 2.31 × 10-3 mg/ml) and the ethanolic extract of Bergenia ligulata (IC50 = 3.20 × 10-3 mg/ml) inhibited the neuraminidase best. Extracts of Echinacea angustifolia, Eleuterococcus senticosus and Zingiber officinale exhibited weak inhibitory activities. This leads to the conclusion that natural products and plant extracts seem to be a promising source in finding new neuraminidase inhibitors.

Literatur

  • 1 Ba Y, Keli P. Colour Atlas of Chinese Traditional Drugs. Beijing; Sience Press 1987
  • 2 Chattopadhyay D, Naik T. Antivirals of ethnomedicinal origin: Structure-activity relationship and scope.  Mini Rev Med Chem. 2007;  7 275-301
  • 3 Chevallier A. Das große Lexikon der Heilpflanzen. München/Starnberg; Dorling Kindersley Verlag 2001
  • 4 Cook G, Zumla A. Manson’s Tropical Diseases. 21. ed. London; W.B. Saunders 2004
  • 5 Flint S, Enquist L, Racaniello V, Skalka A. Principles of Virology. 2. ed. Washington; ASM Press 2004
  • 6 Hatakeyama S, Sugaya N, Ito M, Yamazaki M, et al.. Emergence of influenza B virus with reduced sensitivity to neuraminidase inhibitors.  JAMA. 2007;  297 1435-1442
  • 7 Hurt A, Iannello P, Jachno K, Komadina N, et al.. Neuraminidase inhibitor-resistant and -sensitive influenza B viruses isolated from an untreated human patient.  Antimicrob Agents Chemother. 2006;  50 1872-1874
  • 8 Itzstein M von, Wu W-Y, Kok G, Pegg M, et al.. Rational design of potent sialidase-based inhibitors of influenza virus replication.  Nature. 1993;  363 418-423
  • 9 Li B, Fu T, Dongyan Y, Mikovits J, et al.. Flavonoid baicalin inhibits HIV-1 infection at the level of viral entry.  Biochem Biophys Res Commun. 2000;  276 534-538
  • 10 Ma S, Du J, But P, Deng X, et al.. Antiviral Chinese medicinal herbs against respiratory syncytial virus.  J Ethnopharmacol. 2002;  79 205-211
  • 11 McKimm-Breschin J, Trivedi T, Hampson A, Hay A, et al.. Neuraminidase sequence analysis and susceptibilities of influenza virus clinical isolates to zanamivir and oseltamivir.  Antimicrob Agents Chemother. 2003;  47 2264-2272
  • 12 Miki K, Nagai T, Suzuki K, Tsujimura R, et al.. Anti-influenza virus activity of biflavonoids.  Bioorg Med Chem Lett. 2007;  17 772-775
  • 13 Modrow S, Falke D, Truyen U. Molekulare Virologie. 2. Aufl. Heidelberg; Spectrum Akademischer Verlag 2003
  • 14 Nagai T, Yamada H, Otsuka Y. Inhibition of mouse liver sialidase by the root of Scutellaria baicalensis .  Planta Med. 1989;  55 27-29
  • 15 Nagai T, Miyaichi Y, Tomimori T, Suzuki Y, Yamada H. Inhibition of influenza virus sialidase and anti-influenza virus activity by plant flavonoids.  Chem Pharm Bull. 1990;  38 1329-1332
  • 16 Nagai T, Miyaichi Y, Tomimori T, Suzuki Y, Yamada H. In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase.  Antiviral Res. 1992;  19 207-217
  • 17 Nagai T, Moriguchi R, Suzuki Y, Tomimori T, Yamada H. Mode of action of the antiinfluenza virus activity of plant flavonoid, 5,7,4’-trihydroxy-8-methoxyflavone, from the roots of Scutellaria baicalensis .  Antiviral Res. 1995;  26 11-25
  • 18 Ohuchi M, Asaoka N, Sakai T, Ohuchi R. Roles of neuraminidase in the initial stage of influenza virus infection.  Microbes Infect. 2006;  8 1287-1293
  • 19 Osawa K, Yasuda H. Macrocarpals h, i, and j from the leaves of Eucalyptus globulus .  J Nat Prod. 1996;  59 823-827
  • 20 Park KJ. Evaluation of in vitro antiviral activity in methanol extracts against influenza virus type A from Korean medicinal plants.  Phytother Res. 2003;  17 1059-1063
  • 21 Potier M, Mameli L, Bélisle M, Dallaire L, Melancon S. Fluorometric assay of neuraminidase with sodium (4-methylumbelliferyl-α-D-N-acetylneuraminate) substrate.  Anal Biochem. 1979;  94 287-296
  • 22 Rajbhandari M, Wegner U, Jülich M, Schöpke T, Mentel R. Screening of Nepalese medicinal plants for antiviral activity.  J Ethnopharmacol. 2001;  74 251-255
  • 23 Rameix-Welti M, Agou F, Buchy P, Mardy S, et al.. Natural variation can significantly alter the sensitivity of influenza A (H5N1) viruses to oseltamivir.  Antimicrob Agents Chemother. 1996;  50 3809-3815
  • 24 Reid A, Taubenberger J, Fanning T. The 1918 Spanish influenza integrating history and biology.  Microbes Infect. 2001;  3 81-87
  • 25 Schönfelder I, Schönfelder P. Das neue Handbuch der Heilpflanzen. Stuttgart; Franckh-Kosmos Verlag 2004
  • 26 Serkedjieva J, Manolova N. Plant phenolic complex inhibits the reproduction of influenza and herpes simplex viruses.  Basic Life Sci. 1992;  59 705-715
  • 27 Sokmen M, Angelova M, Krumova E, Pashova S, et al.. In vitro antioxidant activity of polyphenol extracts with antiviral properties form Geranium sanguineum L.  Live Sci. 2005;  76 2981-2993
  • 28 Teuscher E, Melzig M, Lindequist U. Biogene Arzneimittel. 4. Aufl. Stuttgart; Wissenschaftliche Verlagsgesellschaft 2004
  • 29 Yen H, Hoffmann E, Taylor G, Scholtissek C, et al.. Importance of neuraminidase activesite residues to the neuraminidase inhibitor resistence of influenza viruses.  J Virol. 2006;  80 8787-8795
  • 30 Ying L, Gervay-Hague J. One-bead-oneinhibitor-one-substrate screening of neuraminidase activity.  ChemBioChem. 2005;  6 1857-1865

Prof. Dr. Matthias F. Melzig

Sverre Morten Schwerdtfeger

Freie Universität Berlin

Institut für Pharmazie

Königin-Luise-Str. 2+4

14195 Berlin

Email: melzig@zedat.fu-berlin.de

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