Planta Med 2001; 67(9): 825-832
DOI: 10.1055/s-2001-18850
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Antileishmanial Activity of Hydrolyzable Tannins and their Modulatory Effects on Nitric Oxide and Tumour Necrosis Factor-α Release in Macrophages in Vitro

H. Kolodziej1 , O. Kayser2 , A. F. Kiderlen3 , H. Ito4 , T. Hatano4 , T. Yoshida4 , L. Y. Foo5
  • 1 Institut für Pharmazie, Pharmazeutische Biologie, Freie Universität Berlin, Berlin, Germany
  • 2 Institut für Pharmazie, Pharmazeutische Technologie, Biopharmazie und Biotechnologie, Freie Universität Berlin, Berlin, Germany
  • 3 Robert Koch-Institut, Abteilung für Infektionskrankheiten, Berlin, Germany
  • 4 Faculty of Pharmaceutical Sciences, Okayama University, Okayama, Japan
  • 5 New Zealand Institute for Industrial Research, New Zealand
Further Information

Publication History

December 28, 2000

March 21, 2001

Publication Date:
06 December 2001 (online)

Abstract

A series of 27 hydrolyzable tannins and related compounds was tested for antiparasitic effects against both extracellular promastigote and intracellular amastigote Leishmania donovani organisms. In parallel, the compounds were evaluated for their immunomodulatory effects on macrophage functions, including release of nitric oxide (NO), tumour necrosis factor-α (TNF-α) and interferon (IFN)-like properties using several functional assays. Of the series of polyphenols tested, only gallic acid (54 μM NO) and its methyl ester (32 μM NO) induced murine macrophage-like RAW 264.7 cells to release NO in appreciable amounts (IFN-γ/LPS 119 μM NO). The in vitro TNF-inducing potential of the polyphenols examined increased in the order of oligomeric ellagitannins (EC50 > 25 μg/ml) < monomeric ellagitannins, gallotannins (EC50 8.5 to > 25 μg/ml) < C-glucosidic ellagitannins, dehydroellagitannins (EC50 0.6 - 2.8 μg/ml) at the host cell subtoxic concentration of 50 μg/ml. Furthermore, promastigotes of Leishmania donovani were assayed in the presence of these polyphenols and the results showed that none of the compounds was significantly toxic (EC50 > 25 μg/ml) to the extracellular forms. In contrast, all polyphenols showed pronounced antileishmanial activities (EC50 < 0.4 - 12.5 versus 7.9 μg/ml for Pentostam®) against intracellular amastigotes of L. donovani residing within RAW cells. Noteworthy, most compounds exhibited low cytotoxicity against the murine host cells (EC50 >25 μg/ml). Furthermore, some ellagitannins and the majority of dehydroellagitannins induced potent interferon-like activities as reflected by inhibition of the cytopathic effect of encephalomyocarditis virus on fibroblast L929 cells. This is the first report on hydrolyzable tannins as a new class of natural products with leishmanicidal activity including their potential for inducing the release of NO, TNF and IFN-like activity in macrophage-like RAW cells.

References

  • 1 Porter L J, Hemingway R W. Significance of the condensed tannins. In : Rowe JW, editor Natural products of woody plants II. Berlin; Springer 1989: 988-1027
  • 2 Haslam E, Lilley T H, Cai Y, Martin R, Magnolato D. Traditional herbal medicines - the role of polyphenols.  Planta Medica. 1989;  55 1-8
  • 3 Haslam E. Natural polyphenols (vegetable tannins) as drugs: possible modes of action.  Journal of Natural Products. 1996;  59 205-5
  • 4 Kolodziej H, Kayser O, Latté K P, Ferreira D. Evaluation of the antimicrobial potency of tannins and related compounds using the microdilution broth method.  Planta Medica. 1999;  65 444-6
  • 5 Kayser O, Kolodziej H ., Kiderlen A F. Immunomodulatory principles of Pelargonium sidoides .  Phytotherapy Research. 2001;  15 122-6
  • 6 Kolodziej H, Kayser O, Latté K P, Kiderlen A F. Enhancement of antimicrobial activity of tannins and related compounds by immune modulatory effects. In: Gross GG, Hemingway RW, Yoshida T, editors Plant Polyphenols 2: Chemistry, Biology, Pharmacology, Ecology. New York; Kluwer Academic/Plenum Publishers 1999: 575-94
  • 7 Okuda T, Yoshida T, Hatano T. Hydrolyzable tannins and related polyphenols.  Progress in the Chemistry of Organic Natural Products. 1995;  66 1-117
  • 8 Latte K P, Kolodziej H. Pelargoniins, new ellagitannins from Pelargonium reniforme .  Phytochemistry. 2000;  54 701-8
  • 9 Foo L Y. Amariin, a di-dehydrohexahydroxydiphenoyl hydrolysable tannin from Phyllanthus amarus .  Phytochemistry. 1993;  37 487-91
  • 10 Kayser O, Kiderlen A F, Folkens U, Kolodziej H. In vitro leishmanicidal activity of aurones.  Planta Medica. 1999;  65 316-9
  • 11 Kiderlen A F, Kaye P M. A modified colorimetric assay of macrophage activation for intracellular cytotoxicity against Leishmania parasites.  Journal of Immunological Methods. 1990;  127 11-7
  • 12 Kiderlen A F. Methodensammlung. Robert Koch-Institut Berlin, Germany; 1996
  • 13 Algermissen B, Nündel M, Riedel E. Analytik von Aminosäuren mit Fluoreszenz-HPLC.  GIT Fachzeitschrift für das Laboratorium. 1980;  30 783-90
  • 14 Marcucci F, Klein B, Kirchner M ., Zawatzky R. Production of high titers of interferon gamma by prestimulated spleen cells.  European Journal of Immunology. 1982;  12 787-90
  • 15 James S L. Role of nitric oxide in parasitic infections.  Microbiological Reviews. 1995;  59 533-47
  • 16 Beutler B, Cerami A. The biology of cachectin/TNF: a primary mediator of host response against a human tumour necrosis factor-α receptor.  Annual Review of Immunology. 1989;  7 625-55
  • 17 Zidek Z, Tuckova L, Mara M, Barot-Ciorbaru R, Prokesova L, Tlaskalova-Hogenova H. Stimulation of macrophages by Bacillus firmus: production of nitric oxide and cytokines.  International Journal of Immunopharmacology. 1998;  20 359-68
  • 18 Gessani S, Belardelli F. IFN-γ expression in macrophages and its possible biological significance.  Cytokine & Growth Factor Reviews. 1998;  9 117 -23

Prof. Dr. H. Kolodziej

Institut für Pharmazie

Pharmazeutische Biologie

Freie Universität Berlin

Königin-Luise-Str. 2+4

14195 Berlin

Germany

Email: kolpharm@zedat-fu-berlin.de

Fax: +49 (0) 30-838-53729