Immune-mediated parasite clearance in mice infected with Plasmodium berghei treatment with manzamine A.

Department of Biological Sciences, National University of Singapore, Singapore.
Parasitology Research (Impact Factor: 2.33). 10/2001; 87(9):715-21. DOI: 10.1007/s004360000366
Source: PubMed

ABSTRACT Manzamine A, a sponge-derived alkaloid, was recently shown to possess in vivo antimalarial activity against the blood stages of the rodent malaria parasite Plasmodium berghei. A single intraperitoneal dose of 100 micromol/kg of manzamine A suppressed parasite growth but was followed by parasite recrudescence. Forty percent of mice with recrudescing parasites were able to recover and clear the fulminating parasitaemia. Examination of sera from these mice revealed that infected mice treated with manzamine A had a suppressed IFN-gamma production but an increase in their IL-10 and IgG production. The prolonged survival of infected mice treated with manzamine A and the eventual clearance of recrudescing parasites in some of these mice involve a down-regulation of Thl responses and a switch to antibody dependent-Th2 responses.

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    • "The biological activities of new metabolites from sponges have been reported in hundreds of scientific papers. Sponges have the potential to provide future drugs against important diseases such as cancer (Bai et al. 1993; Blackburn et al. 1999; Hood et al. 2002; Molinski et al. 2009), inflammation (Tan et al. 1997; Pope et al. 1999; Festaa et al. 2012), cardiovascular (Maryanoff et al. 1993; Shuman et al. 1993; Chackalamannil 2001), viral (Müller et al. 1987; Ford et al. 1999; Wellington et al. 2000), plasmodial (Ang et al. 2001) and bacterial (D_Ambrosio et al. 1996). Previous work on another species of the genus Dragmacidon collected from Andaman Sea in Thailand resulted in the isolation of a number of b-carboline alkaloids; some of them are characterised by possessing potent anti-inflammatory and antitumour activities (Pedpradab et al. 2004). "
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    ABSTRACT: Chemical investigation of the Red Sea sponge Dragmacidon coccinea led to the isolation of a new nucleoside, dragmacidoside (1), along with eight known compounds: adenosine (2), inosine (3), deoxycytidine (4), methyl-α-d-glucopyranoside (5), clionasterol (6), stigmasterol (7), campesterol (8) and brassicasterol (9). The compounds were isolated from chloroform and ethyl acetate fractions of the methanolic extract of the sponge, and their structures were established based on various spectroscopic data including MS, 1D and 2D NMR (COSY, HSQC and HMBC). Biological testing revealed that the chloroform fraction possesses significant anti-inflammatory activity in the carrageenan-induced hind paw oedema in rats.
    Natural product research 05/2014; 28(15):1-8. DOI:10.1080/14786419.2014.915828 · 1.23 Impact Factor
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    • "Youssaf et al., 2002). This antimalarial effect of manzamine-A is due to an enhanced immune response (Ang et al., 2001). "
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    ABSTRACT: Malaria, which is caused by multiplication of the protozoan parasite Plasmodium falciparum in erythrocytes, is a major health problem in many southern countries. There is an urgent need to discover new antimalarials, due to the spread of chloroquinine resistance and the limited number of available drugs. Among marine invertebrates, Porifera (sponges) are potential source of novel bioactive compounds to provide future drugs against malaria, cancer and a range of viral diseases. A number of sponge-derived antimalarials have been discovered during the last decade. The compounds are mostly nitrogen containing ones (proteins, pyridines, tyrosine-based metabolites, alkaloids, indoles and amides) and also non-nitrogenous compounds (terpenes, polyketides and polysaccharides).
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    ABSTRACT: Le paludisme est causé par le parasite hématozoaire Plasmodium. Sérieux problème de santé publique, il provoque de nombreux décès, surtout chez les enfants de moins de cinq ans des zones tropicales. Les traitements classiques deviennent inefficaces à cause des résistances du parasite. L'urgence est la découverte de nouvelles molécules. Les ressources naturelles (dont proviennent quinine et artémisinine, antipaludiques majeurs), et parmi elles les organismes marins, sont une source potentielle de molécules. La girolline, connue pour ses propriétés antitumorales, est extraite de l'éponge Cymbastela cantharella. Nous avons étudié sa capacité à inhiber la croissance du Plasmodium in vitro et in vivo, son mode d'action et sa potentialisation avec la chloroquine (antipaludique de référence). Nous avons aussi évalué sa toxicité cellulaire et murine (aiguë) et l'activité de quelques dérivés. Excellent antipaludique, la girolline peut devenir le chef de file d'une nouvelle classe de molécules.
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