Abstract
Red algae-derived bioactive oligosaccharides have drawn increasing attention in drug discovery, yet their therapeutic potential in crystal-induced inflammation remains underexplored. Here, we investigated the anti-inflammatory effects and underlying mechanisms of neoagarohexaose (NA6), a well-defined agarose-derived oligosaccharide, in a mouse model of acute monosodium urate (MSU)-induced paw inflammation—a widely used surrogate of acute gout flares—and in RAW264.7 macrophages. Topical application of NA6 significantly alleviated paw swelling and subcutaneous tissue damage and was accompanied by reduced circulating myeloperoxidase activity and pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) at 24 h; under the present conditions, the high-dose NA6 group did not differ significantly from the diclofenac emulgel group. Immunofluorescence and qRT-PCR analyses confirmed reduced cytokine expression in paw tissues. Transcriptomic profiling and network analysis identified Ccl2 as the chemokine most strongly suppressed following NA6 treatment. In vitro, NA6 reduced MSU-induced Ccl2 expression and CCL2 secretion in macrophages, which was accompanied by reduced chemotactic migration, an effect partially reversed by recombinant CCL2 supplementation. Collectively, these findings show that topical NA6 alleviates acute MSU-induced paw inflammation and that this effect is accompanied by reduced CCL2 production and CCL2-associated chemotactic activity, supporting NA6 as a marine-derived candidate worthy of further investigation for the topical management of gout flares.