Sustainable biovalorization of invasive Sargassum horneri: Dual immunomodulatory and gut-protective effects of sulfated polysaccharides in zebrafish and Caco-2 models

Inflammatory bowel disease (IBD) is a chronic condition characterized by persistent intestinal inflammation and disruption of the epithelial barrier, with limited effective treatments currently available. The present study was designed to assess the immunomodulatory and intestinal barrier-protective effects of sulfated polysaccharides extracted from Sargassum horneri (SHCPs) using both in vitro Caco-2 cell models and an in vivo dextran sulfate sodium (DSS)-induced zebrafish colitis model. SHCPs exhibited moderate activation of the NF-κB signaling pathway, which facilitated the balanced upregulation of key cytokines IL-6, IL-8, and IL-10, enhancing mucosal immune readiness without eliciting harmful inflammation. In Caco-2 cells, SHCPs significantly protected against DSS-induced decreases in cell viability and attenuated the DSS-induced upregulation of pro-inflammatory mediators, including PGE₂, TNF-α, IL-6, and IL-1β. Zebrafish treated with SHCPs demonstrated reduced intestinal epithelial cell death, diminished nitric oxide production, attenuation of mucus hypersecretion, and improved gut motility, collectively mitigating hallmark features of IBD pathology. These bioactivities are closely linked to the distinct sulfation patterns and fucosylated backbone of SHCPs. Taken together, our findings highlight SHCPs as promising natural marine polysaccharides with the potential to restore intestinal immune homeostasis and alleviate inflammation-related gut disorders. Further investigations involving mammalian systems and clinical trials are necessary to validate their efficacy and clarify the underlying molecular mechanisms.