ABSTRACT
The present study investigated in vitro the effects of sulphated heterorhamnan (Go3), iota-/nu-carrageenans (G3d and EHW-I) and arabinogalactan (ARAGAL) polysaccharides on macrophage activation and inhibition of intracellular amastigotes of Leishmania (L.) amazonensis. All the sulphated polysaccharides (Go3, G3d and EHW-I) promoted increased nitric oxide production varying from 71 to 110%. The leishmanicidal activity of all compounds was compared to the inhibition effect of Meglumine Antimoniate at 300µg/mL (â¼79%), used as positive control. Inhibition of Leishmania (L.) amazonensis growth was 55% with 5µg/mL of Go3, 50% and 98% to G3d and EHW-I, respectively at 10µg/mL, and 88% with 10µg/mL of ARAGAL. The superoxide anion scavenging activity for the sulphated polysaccharides varied from approximately 30-55% at 10µg/mL. In conclusion, the results of the present study indicate the promising potential of these polysaccharides for the development of new alternative therapeutic agents against leishmaniasis.
Subject(s)
Leishmania/drug effects , Polysaccharides/chemistry , Polysaccharides/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/pharmacology , Animals , Cytotoxicity, Immunologic/drug effects , Leishmania/metabolism , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/parasitology , Mice , Nitric Oxide/biosynthesis , Parasitic Sensitivity Tests , Superoxides/metabolismABSTRACT
Storage xyloglucans from the seeds of Copaifera langsdorffii, Hymenaea courbaril and Tamarindus indica were obtained by aqueous extraction from the milled and defatted cotyledons, XGC, XGJ and XGT, respectively. The resulting fractions showed similar monosaccharide composition with Glc:Xyl:Gal molar ratios of 2.4:1.5:1.0, 3.8:1.5:1,0 and 3.6:2.4:1.0 for XGC, XGJ and XGT, respectively. High-performance size-exclusion chromatography of the polysaccharides showed unimodal profiles, and the average molar mass (M(w)) was obtained for XGC (9.6 × 105 g/mol), XGJ (9.1 × 105 g/mol) and XGT (7.3 × 105 g/mol). The immunomodulatory effects of the xyloglucans on peritoneal macrophages were evaluated. Phagocytic activity was observed in macrophages treated with XGT. The effect of XGT was tested on the production of O2(.-) and NO. At 25 µg/ml XGT caused a 100% increase in NO production when compared to the control group; however, it did not affect O2(.-) production in the absence of PMA. The production of TNF-α, interleukins 1ß and 6 by macrophages in the presence of the xyloglucans was evaluated. The polysaccharides affected the production of the cytokines by macrophages to different degrees. XGC caused an enhancement of IL-1ß and TNF-α production, compared to the other xyloglucans. For IL-6 production, XGT gave greater stimulation than XGC and XGJ, reaching 87% at 50 µg/ml. XGJ promoted a statistically significant effect on all cytokine productions tested. The results indicate that the xyloglucans from C. langsdorffii, H. courbaril and T. indica can be classified as biological response modifiers (BRM).
