Anti-inflammatory potential of sulfated heteropolysaccharide from marine pharaoh cuttlefish Sepia pharaonis on LPS-activated THP-1 monocytes and RAW 264.7 macrophages

Pai, Shilpa K and Chakraborty, Kajal (2025) Anti-inflammatory potential of sulfated heteropolysaccharide from marine pharaoh cuttlefish Sepia pharaonis on LPS-activated THP-1 monocytes and RAW 264.7 macrophages. Food Research International, 221 (1). pp. 1-14.

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Abstract

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.

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