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2001 (1)
1Author    AlbrechtF. Kiderlen3, Oliver Kayserb, Daneel Ferreirac, H. Erbert KolodziejdRequires cookie*
 Title    Tannins and Related Compounds: Killing of Amastigotes of Leishmania donovani and Release of Nitric Oxide and Tumour Necrosis Factor a in Macrophages in vitro  
 Abstract    The antileishmanial and immunomodulatory potencies of a series of 28 polyphenols were evaluated in terms of extra-and intracellular leishmanicidal activity and macrophage activa­ tion for release of nitric oxide (N O), tumour necrosis factor (TNF) and interferon (IFN)-like properties. For this, several functional bioassays were employed including an in vitro model for leishmaniasis in which murine bone marrow-derived macrophages (B M M $) were infected with the obligate intracellular parasite Leishmania donovani, an extracellular Leish­ mania proliferation assay, a fibroblast-lysis assay (TNF-activity), and a biochemical assay for NO. Except for gallic acid, its methyl ester, shikimic acid and catechin (EC50 2 5 .8 -6 7 .9 nM) all polyphenols tested significantly inhibited the intracellular survival of L. donovani amasti­ gotes (EC 50 0 .4 -1 3 .9 nM) when compared with the clinically used agent, sodium stibogluco­ nate (EC 50 10.6 nM). In contrast, none of the samples proved to be directly toxic for the extracellular promastigote form of the parasite. Noteworthy, the phenolic samples showed only moderate or no cytotoxicity against the murine host cells (EC 50 10 to >144 nM). A l­ though NO is an important effector molecule in macrophage microbicidal activity, the induc­ ing potential of the test com pounds for its release was found to be very moderate ranging from 7 -5 4 jam (IFN-y/LPS 119 (.im). On the other hand, inhibition of NO production had no apparent effect on intracellular leishmanicidal activity of polyphenols. Their in vitro TNF-inducing potential producing 50% lysis in murine L929 cells increased in the order o f simple phenols and flavanols (3 4 -4 8 U /m l) < A -type proanthocyanidins (5 3 -8 0 U/m l) < B-type proanthocyanidins (6 4 -2 0 0 U /m l) < hydrolyzable tannins (2 8 7 -3 5 0 U/ml) at the host cell subtoxic concentration of 50 ^g/ml. Furthermore, gallic acid and some hydrolyzable tannins showed appreciable IFN-like activities (1 4 -2 3 U/m l) as reflected by inhibition of the cyto-pathic effect of encephalom yocarditis virus on fibroblast L 929 cells. The results provide a rational basis for the recorded anti-infectious efficacy o f traditionally used herbal medicines containing tannins in vivo, in the light of both only moderate direct antimicrobial activities of distinct polyphenols in vitro and the limited knowledge on their uptake in humans. 
  Reference    Z. Naturforsch. 56c, 444 (2001); received February 9/March 8 2001 
  Published    2001 
  Keywords    Polyphenols, Leishmania don ovan i, Immunomodulation, Tumour Necrosis Factor 
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 TEI-XML for    default:Reihe_C/56/ZNC-2001-56c-0444.pdf 
 Identifier    ZNC-2001-56c-0444 
 Volume    56