Biology Reference
In-Depth Information
with the obligate intracellular parasite, all of the gallotannins and
ellagitannins (monomers to trimers) showed pronounced antileishmanial
effects against
L
.
donovani
intracellular amastigotes with EC
50
< 0.4-7.5
μg/ml. Most of the compounds tested had low cytotoxicity (EC
50
> 25
μg/ml) against the murine host cells.
The dehydroellagitannins geraniin (
19
), phyllanthusiin B (
33
)
and elaeocarpusin (ascorgeraniin,
39
) and the gallotannins
pentagalloylglucose (PGG,
9
) and tannic acid exhibited the most potent
antileishmanial effect with EC
50
< 0.4 μg/ml, which is comparable to that
of the widely used therapeutic drug amphotericin B (EC
50
= 0.3 μg/ml).
Casuarinin (
45
) and castalagin (
43
) also showed potent effects with EC
50
of 0.5 and 2.7 μg/ml, respectively. In contrast, none of the compounds
were toxic to extracellular promastigotes (EC
50
> 25 μg/ml).
The intracellular amastigote-specific effect of ellagitannins was
associated with immunomodulatory effects of the tannins on macrophage
functions, as shown in several functional assays. These assays evaluated
the release of nitric oxide (NO), tumor necrosis factor-α (TNF-α) and
interferon (IFN) in the presence of each tannin. Among the cytokines
induced by tannins, the TNF-α-inducing activity evaluated in an assay
using TNF-sensitive L929 fibroblasts increased in the following order:
oligomeric ellagitannins (EC
50
> 25 μg/ml; inactive) < monomeric
ellagitannins and gallotannins (EC
50
8.5->25 μg/ml) <
C
-glycosidic
ellagitannins and dehydroellagitannins (EC
50
0.6-2.8 μg/ml).
The aforementioned potent leishmanicidal dehydroellagitannins and
C
-glycosidic ellagitannins stimulated macrophages to release significant
amounts of TNF-α, indicating that the antiparasitic effects of the tannins
are due to their immunomodulatory effect, and not to a direct action.
From these
in vitro
results, Kolodziej
et al
. (2001) concluded that
tannins, and in particular ellagitannins, are capable of enhancing
nonspecific immunity
via
macrophage activation and the release of
cytokines, thereby inducing the fundamental host defense system to
destroy invading pathogens. These immunological responses may
account for the effectiveness of traditional polyphenol-rich medicines in
infectious and other diseases.
