Efeito leishmanicida in vitro contra leishmania infantum dos polissacarídeos sulfatados da alga marinha vermelha solieria filiformis

Abstract

Marine algae are essential organism for the maintenance of marine ecosystems and have broad applications in the industrial, biotechnological, and pharmaceutical sectors. Among them, red algae (Rhodophyta) have attracted considerable attention due to their high capacity to produce sulfated polysaccharides (SPs), which are complex macromolecules composed of negatively charged sugar polymers resulting from the presence of sulfate groups in their structure. These compounds exhibit a wide range of biological activities, including antileishmanial effects. In Brazil, visceral leishmaniasis (VL), caused by the protozoan Leishmania infantum, is a neglected and potentially fatal disease. Current treatment relies on meglumine antimoniate and amphotericin B, which are associated with significant adverse effects and the emergence of drug-resistant strains. Therefore, the search for novel biomolecules with antileishmanial potential is of great importance. In this context, the present study aimed to evaluate the in vitro leishmanicidal activity of sulfated polysaccharides extracted from the red marine alga Solieria filiformis (SPf) against L. infantum. SPf were extracted by proteolytic digestion with papain (60 °C for 6 h). Subsequently, promastigote forms (107 cells/mL) were incubated with SPf at concentrations of 5, 10, 25, and 50 μg/mL for 24 and 48 h. To evaluate the effects against amastigote forms, J774 macrophages infected with promastigotes (107 parasites/mL; parasite-to-macrophage ratio of 10:1) were treated with SPf for 24 and 48 h. After the incubation periods, culture supernatants were collected for nitric oxide (NO) quantification, and parasite burden was determined. Data were expressed as mean ± standard error of the mean (SEM) and analyzed by one-way analysis of variance (ANOVA) followed by Tukey's test (p < 0.05). A significant reduction in promastigote viability was observed only after 48 h of treatment at all tested concentrations (42.29% ± 5.95, 39.54% ± 2.09, 37.30% ± 3.99, and 29.71% ± 4.55, respectively). In contrast, all SPf concentrations significantly reduced the number of intracellular amastigotes at both time points (24 h: 47.8% ± 5.1, 51.4% ± 2.6, 42.8% ± 4.2, and 34.0% ± 2.3; 48 h: 59.0% ± 1.9, 52.7% ± 4.6, 51.1% ± 6.0, and 51.4% ± 5.9, respectively). This anti-amastigote activity is associated with an immunomodulatory mechanism, as treatment with SPf significantly increased NO production, suggesting that these sulfated polysaccharides have potential as therapeutic agents for the control of VL. Nevertheless, further studies are required to elucidate the underlying mechanisms of action of these biomolecules.