Anti-inflammatory potential of sulfated heteropolysaccharide from marine pharaoh cuttlefish Sepia pharaonis on...

Sepia pharaonis, the marine pharaoh cuttlefish, is highly valued in the seafood industry for its nutritional richness, culinary delicacy, and bioactive ingredients. The upregulation of inflammation-related chemokines, cytokines, lipid mediators, and reactive oxygen species plays a crucial role in both acute and chronic inflammation. Recently, marine-derived sulfated polysaccharides have emerged as potent anti-inflammatory agents owing to their structural diversity in attenuating inflammatory cytokines. In this direction, a sulfated heteropolysaccharide (SPP-1) was isolated from the edible portion of the cuttlefish Sepia pharaonis, and characterized as [→4)-β-Galp-{(1 → 3)-3-O-SO₃-α-GlcAp}-(1 → 4)-3-O-SO₃-β-Manp-(1→]. SPP-1 demonstrated potential anti-inflammatory effects by attenuating pro-inflammatory enzymes using in vitro chemical models and cytokine levels in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages and human THP-1 monocytes. In LPS-stimulated RAW 264.7 cells, SPP-1 effectively attenuated the release of key inflammatory mediators, including interleukins (IL)-6 and IL-1β, nitric oxide (NO), and tumor necrosis factor-alpha (TNF-α), along with downregulating the gene expression of these inflammatory markers. SPP-1 exhibited comparable effects in THP-1 cells, reducing the production of IL-1β, IL-12, and TNF-α by 79.6 %, 34.5 %, and 79.3 %, respectively, while increasing transforming growth factor (TGF-β) expression by 12-fold compared to LPS treatment. SPP-1 also exhibited significant inhibition of LPS-stimulated NO and IL-6 levels, reducing them by 75-80 %. Gene expression analysis showed a significant downregulation of inflammatory mediators in THP-1 cells, with IL-2 and IFN-γ expression reduced by 2.09-fold and 3.01-fold, respectively. The structure-activity relationship suggests that the anti-inflammatory potential of SPP-1 is largely attributed to its favorable electronic properties, notably the presence of 3-O-sulfation and specific monosaccharide components. Thus, the SPP-1 polysaccharide studied here may serve as a potential pharmacophore lead for the development of interventions targeting inflammation and oxidative stress.