Elucidation of Molecular Mechanisms of Sulfated Oligoguluronic Acid on Mitigating Intestinal Inflammation and Enhancing Epithelial Barrier Function

This study investigates the protective role of sulfated oligoguluronic acid (SOGA), synthesized from polyguluronic acid (PG)-derived oligoguluronic acid (OGA), against intestinal inflammation and barrier dysfunction. <i>In vitro</i>, SOGA significantly reduced LPS-induced proinflammatory cytokine secretion in THP-1 cells, whereas PG and OGA were ineffective. Mechanistic investigations revealed that SOGA effectively inhibited the activation of LPS-induced NF-κB, JNK MAPK, and NLRP3 inflammasome signaling pathways. In Caco-2 monolayers, SOGA effectively restored mitochondrial function, preserved tight junction integrity, and reduced paracellular permeability. In comparison, this effect was absent for PG and OGA. Additionally, SOGA significantly suppressed the secretion of proinflammatory cytokines in a coculture model of Caco-2/THP-1 cells. <i>In vivo</i>, SOGA ameliorated ulcerative colitis symptoms in mice by reducing inflammation, enhancing tight junction protein expression, and improving mitochondrial function. These findings underscore the potential of SOGA in inflammatory bowel disease treatment by targeting key aspects of inflammation and intestinal barrier dysfunction.