Abstract:
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The antimalarial activity of heparin, against which there are no
resistances known, has not been therapeutically exploited due to
its potent anticoagulating activity. Here, we have explored the
antiplasmodial capacity of heparin-like sulfated polysaccharides
from the sea cucumbers Ludwigothurea grisea and Isostichopus
badionotus, from the red alga Botryocladia occidentalis, and
from the marine sponge Desmapsamma anchorata. In vitro
experiments demonstrated for most compounds significant
inhibition of Plasmodium falciparum growth at low-anticoagulant
concentrations. This activity was found to operate through
inhibition of erythrocyte invasion by Plasmodium, likely
mediated by a coating of the parasite similar to that observed
for heparin. In vivo four-day suppressive tests showed that
several of the sulfated polysaccharides improved the survival of
Plasmodium yoelii-infected mice. In one animal treated with I.
badionotus fucan parasitemia was reduced from 10.4% to
undetectable levels, and Western blot analysis revealed the
presence of antibodies against P. yoelii antigens in its plasma.
The retarded invasion mediated by sulfated polysaccharides, and
the ensuing prolonged exposure of Plasmodium to the immune
system, can be explored for the design of new therapeutic
approaches against malaria where heparin-related polysaccharides
of low anticoagulating activity could play a dual role as drugs
and as potentiators of immune responses. |