Mechanistic Insights into the Anti-Inflammatory Activity of a Sulfated α-Glucan (VpG) from Volutharpa ampullacea perryi

A novel sulfated α-glucan (VpG), with an ultra-high molecular weight of approximately 2250 kDa and a sulfation degree of 18.6%, was previously isolated from Volutharpa ampullacea perryi and shown to alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. However, the underlying mechanisms remain unclear. In the present study, we further characterized the structural features of VpG using scanning electron microscopy (SEM), atomic force microscopy (AFM) and UV-Vis spectroscopy, and evaluated its immunomodulatory effects in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. SEM revealed a dense, porous surface with co-existing filamentous and flake-like structures, while AFM imaging showed that VpG adopted an irregular branched chain-like conformation. In functional assays, VpG significantly inhibited the production of pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and toll-like receptor 4 (TLR4) in a dose-dependent manner. Flow cytometric analysis revealed that VpG downregulated LPS-induced expression of the M1 surface marker CD80, while Western blotting showed that VpG suppressed the phosphorylation of p38, ERK1/2, and JNK1/2/3, indicating blockade of the MAPK signaling pathway. In addition, VpG exhibited potent radical scavenging activity against hydroxyl and superoxide anion radicals, which is associated with its anti-inflammatory activity. Collectively, these findings indicate that VpG exerts its anti-inflammatory effects through the inhibition of M1 macrophage polarization and suppression of MAPK activation, with its antioxidant capacity potentially contributing to the overall effect. This study provides a mechanistic basis for understanding the anti-inflammatory action of VpG and supports its potential as a therapeutic candidate for ulcerative colitis.