title: Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium.
abstract: 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.
authors.affiliation: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.|Barcelona Institute for Global Health (ISGlobal), Barcelona Center for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain.|Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Spain.
authors.forename: Joana
authors.initials: J
authors.lastname: Marques
authors.affiliation: Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vilanova
authors.affiliation: Hospital Universitário Clementino Fraga Filho and Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Paulo A S
authors.initials: PA
authors.lastname: Mourão
authors.affiliation: Nanomalaria Group, Institute for Bioengineering of Catalonia (IBEC), Barcelona, Spain.|Barcelona Institute for Global Health (ISGlobal), Barcelona Center for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain.|Nanoscience and Nanotechnology Institute (IN2UB), University of Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Fernàndez-Busquets
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000469:parasitology; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology; D010967:Plasmodium yoelii / Q000187:drug effects* / Q000502:physiology; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D000461:Rhodophyta / Q000737:chemistry*; D013431:Sulfates / Q000737:chemistry
chemical_list: D000962:Antimalarials; D011134:Polysaccharides; D013431:Sulfates