Atividades antiviral e anti-inflamatória de uma fração polissacarídica sulfatada da alga marinha vermelha Gracilaria birdiae (Plastino e Oliveira).

Abstract

Bioactive molecules extracted from seaweed, such as sulfated polysaccharides, have been highlighted as having diverse biological activities. This study aimed to evaluate the antiviral activity and anti-inflammatory effect of a sulfated polysaccharide from seaweed Gracilaria birdiae. Total sulfated polysaccharides (TSP) were extracted by enzimatic digestion and following fractioned on DEAE-cellulose column, obtaining two fractions (FI - 0.5 M and FII - 0.75 M). The FI fraction, which had the highest yield, was object of this study, has been identified as an agar by IR spectroscopy (FT-IR) and with a high molecular weight (>100KDa) by gel permation cromatography. The cell viability of FI fraction was determined by the change of the cell morphology with further quantification at 492 nm. Cells were treated with serial dilutions of FI (1000 to 7.8 μg/mL) and then, neutral red dye was incorporated, with subsequent measurement of absorbance. The degree of antiviral activity was expressed as percent inhibition of the virus. The results showed that FI at a concentration of 250 μg/mL showed no toxicity on C6/36, Vero and HEp-2 cells and had a significant antiviral effect with inhibition of 95.8% against HSV-1, 94.4% against HSV-2 on Vero cells and 89.2% against DENV-1 on C6/36 cells, when compared to the control group. In addition, FI (10 mg /kg) presented anti-inflammatory effect when administered by subcutaneous route (s.c.) in Wistar rats in a model of peritonitis using carrageenan with a flogistic agent or in the paw edema using carrageenan or dextran. FI (10 mg/kg) induced an anti-inflammatory effect by a decrease in the leukocytes into the peritoneal cavity. FI also reduced the paw edema induced by carrageenan in the third hour comproved by the mieloperoxidase quantification and also inhibited the paw edema induced by dextran on the first thirty minutes. To analyze the involvement of the heme oxygenase pathway on antiinflammatory activity of FI, animals were pretreated by s.c. route with an specific inhibitor of heme group (zinc protoporphyrin IX). After inhibition by ZnPP IX, the anti-inflammatory effect of FI on carrageenan-induced paw edema has not been observed. To evaluate the systemic effects, FI (10 mg/kg) was administered by intraperitoneal route in mice in a single dose. The systemic changes were evaluated during 48 h or by repeated dose, once a day for 14 days. The results showed that, FI (10 mg/kg) did not cause mortality or significant changes in the biochemical, hematological and histopathological parameters, considered safe in the tested dose.