Ethnopharmacological basis and combined protection of intestinal barrier function by fucoidan from Sargassum thunbergii and chito-oligosaccharides in DSS-induced colitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Brown seaweeds of the genus Sargassum have long been used in East Asia as traditional remedies for inflammatory conditions, bacterial infections, and cancer. Sargassum thunbergii, a non-edible and underutilized species, is rich in bioactive fucoidan. Chito-oligosaccharides (COS), derived from marine chitin, have also been traditionally associated with intestinal health and inflammation modulation. However, the ethnopharmacological potential of combining S. thunbergii fucoidan (STF) and COS in intestinal inflammatory conditions remains unexplored.

AIM OF THE STUDY: This study aimed to evaluate the combined protective effects of STF and COS on intestinal inflammation and barrier dysfunction, and to elucidate their complementary pharmacological actions using in vitro and in vivo models of dextran sulfate sodium (DSS)-induced intestinal injury.

MATERIALS AND METHODS: DSS-induced Caco-2 cell monolayers were used to assess cytotoxicity, inflammatory mediator production, epithelial barrier integrity, and tight junction protein expression. A DSS-induced zebrafish larval model was employed to evaluate in vivo anti-inflammatory activity, nitric oxide (NO) production, cell death, and mucus homeostasis. STF and COS were tested individually and in combination at different ratios (1:2; 1:1; 2:1), with sulfasalazine and dexamethasone used as reference drugs.

RESULTS: Both STF and COS individually attenuated DSS-induced inflammatory responses by reducing the production of IL-6, IL-8, TNF-α, and PGE2, and partially restoring the expression of tight junction proteins ZO-1 and occludin. Notably, the STF-COS combination at a 2:1 ratio produced greater protective effects than either treatment alone, resulting in a more effective suppression of inflammatory mediators and a marked improvement in epithelial barrier integrity, comparable to conventional anti-inflammatory drugs. In zebrafish larvae, the STF-COS mixture significantly reduced DSS-induced NO overproduction and cell death, while restoring intestinal mucus homeostasis.

CONCLUSION: The enhanced protective effects of the STF-COS combination are likely attributable to their complementary pharmacological properties, with sulfated fucoidan mediating anti-inflammatory activity and low-molecular-weight COS enhancing bioavailability and epithelial repair. These findings provide experimental evidence supporting the ethnopharmacological potential of combined marine-derived polysaccharides as natural therapeutic candidates for intestinal inflammatory disorders.