RSS-Feed abonnieren
DOI: 10.1055/s-2008-1077269
© Sonntag Verlag in MVS Medizinverlage Stuttgart GmbH & Co. KG
Wirkung von Pflanzenextrakten auf die Neuraminidase-Aktivität
Publikationsverlauf
Publikationsdatum:
18. Juni 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.
Schlüsselwörter
Influenzavirus - Grippe - Neuraminidase - traditionelle pflanzliche Drogen
Key words
Influenza virus - neuraminidase - traditional used plants - inhibitory concentration
Literatur
- 1 Ba Y, Keli P. Colour Atlas of Chinese Traditional Drugs. Beijing; Sience Press 1987
MissingFormLabel
- 2
Chattopadhyay D, Naik T.
Antivirals of ethnomedicinal origin: Structure-activity relationship and scope.
Mini Rev Med Chem.
2007;
7
275-301
MissingFormLabel
- 3 Chevallier A. Das große Lexikon der Heilpflanzen. München/Starnberg; Dorling Kindersley Verlag 2001
MissingFormLabel
- 4 Cook G, Zumla A. Manson’s Tropical Diseases. 21. ed. London; W.B. Saunders 2004
MissingFormLabel
- 5 Flint S, Enquist L, Racaniello V, Skalka A. Principles of Virology. 2. ed. Washington; ASM Press 2004
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 13 Modrow S, Falke D, Truyen U. Molekulare Virologie. 2. Aufl. Heidelberg; Spectrum Akademischer Verlag 2003
MissingFormLabel
- 14
Nagai T, Yamada H, Otsuka Y.
Inhibition of mouse liver sialidase by the root of Scutellaria baicalensis
.
Planta Med.
1989;
55
27-29
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 19
Osawa K, Yasuda H.
Macrocarpals h, i, and j from the leaves of Eucalyptus globulus
.
J Nat Prod.
1996;
59
823-827
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 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
MissingFormLabel
- 24
Reid A, Taubenberger J, Fanning T.
The 1918 Spanish influenza integrating history and biology.
Microbes Infect.
2001;
3
81-87
MissingFormLabel
- 25 Schönfelder I, Schönfelder P. Das neue Handbuch der Heilpflanzen. Stuttgart; Franckh-Kosmos Verlag 2004
MissingFormLabel
- 26
Serkedjieva J, Manolova N.
Plant phenolic complex inhibits the reproduction of influenza and herpes simplex viruses.
Basic Life Sci.
1992;
59
705-715
MissingFormLabel
- 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
MissingFormLabel
- 28 Teuscher E, Melzig M, Lindequist U. Biogene Arzneimittel. 4. Aufl. Stuttgart; Wissenschaftliche Verlagsgesellschaft 2004
MissingFormLabel
- 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
MissingFormLabel
- 30
Ying L, Gervay-Hague J.
One-bead-oneinhibitor-one-substrate screening of neuraminidase activity.
ChemBioChem.
2005;
6
1857-1865
MissingFormLabel
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