Objective   To investigate the protective effect and mechanism of fucoidan on intestinal mucosal barrier function in hyperuricemic mice.

  Methods   Forty specific pathogen-free (SPF) C57BL/6J mice were randomly assigned into a control, hyperuricemia model, fucoidan treatment (by gavage administration at the dosage of 200 mg/kg/day continuously for 10 weeks) , and allopurinol positive control group (10 in each group). By the end of the treatments for the mice of the four groups, serum uric acid (UA) was measured with colorimetric method; serum lipopolysaccharides (LPS), diamine oxidase (DAO), tumor necrosis factor (TNF-α) and interleukin-1β (IL-1β) were measured with enzyme-linked immunosorbent assay (ELISA). Histopathological changes in ileum mucosa were observed with hematoxylin-eosin (HE) staining; the expressions of tight junction proteins in ileum mucosa and autophagy-related proteins in small intestine were determined with Western blot.

  Results  Significant decreases in serum UA (52.45%), TNF-α (29.18%), IL-1β (25.36%), LPS (27.24%), and DAO (21.78%) were detected in the hyperuricemic mice with fucoidan treatment ( P < 0.05 for all ); in addition, the fucoidan-treated hyperuricemic mice had significantly improved intestinal cell junctions and permeability, increased expressions of zonula occludens-1 (ZO-l), occludin and autophagy-related proteins (all P < 0.05). Compared to those in model mice, significantly increased ratio of autophagy-related proteins light chain 3B II/I (LC3BII/I), beclin-1, and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) but significantly decreased phosphorylated mammalian target of rapamycin (p-mTOR) were observed in the hyperuricemic mice with fucoidan treatment.

  Conclusion   Oral administration of fucoidan could effectively reduce serum uric acid and improve intestinal mucosal barrier damage by increasing autophagy via p38 MAPK/mTOR pathway in hyperuricemic mice.