The anti-inflammatory mechanisms of the sulfated polysaccharidic fraction obtained from red marine alga Gracilaria cornea (Gc-FI) were investigated using a paw
edema model induced in rats by different inflammatory agents (
carrageenan,
dextran,
serotonin,
bradykinin,
compound 48/80 or
L-arginine). Gc-FI at the doses of 3, 9 or 27 mg/kg, subcutaneously--s.c., significantly inhibited rat paw
edema induced by
carrageenan and
dextran, as confirmed by
myeloperoxidase and
Evans' blue assessments, respectively. Gc-FI (9 mg/kg, s.c.) inhibited rat paw
edema induced by
histamine,
compound 48/80 and
L-arginine. Additionally, Gc-FI (9 mg/kg, s.c.) inhibited Cg-induced
edema in animals with intact mast cells but did not inhibit that with degranulated mast cells by
compound 48/80, revealing a protective role on mast cell membranes. Gc-FI down-regulated the IL-1β, TNF-α and COX-2
mRNA and
protein levels compared with those of the
carrageenan group, based on qRT-PCR and immunohistochemistry analyses. After inhibition with
ZnPP IX, a specific
heme oxygenase-1 (HO-1) inhibitor, the anti-inflammatory effect of Gc-FI was not observed in Cg-induced paw
edema, suggesting that the anti-inflammatory effect of Gc-FI is, in part, dependent on the integrity of the HO-1 pathway. Gc-FI can target a combination of multiple points involved in inflammatory phenomena.