Structure–Function Comparison of Alginate-Derived Oligomannuronic Acid and Mannose in In Vitro and In Vivo Models of Colitis

This study conducts a structural comparison of alginate-derived oligomannuronic acid (MOS) and its monosaccharide analog, mannose, and evaluates their functional differences in colitis intervention. MOS, an oligosaccharide enzymatically prepared from polymannuronic acid, features a unique C4-C5 double bond at the nonreducing end, distinguishing it from the neutral mannose. Functionally, in vitro experiments showed both MOS and mannose significantly suppressed dextran sulfate sodium induced secretion of proinflammatory cytokines in HCoEpiCs. In addition, they restored tight junction (TJ) integrity by inhibiting the MLCK-MLC2 pathway. In vivo, administration of either compound reduced inflammatory cytokine levels, and enhanced TJ protein expression. Notably, MOS demonstrated superior efficacy over mannose at equivalent or lower doses. Mechanistic studies revealed both agents promoted autophagy and suppressed endoplasmic reticulum stress and apoptosis. These findings underscore the contribution of structural features to the enhanced bioactivity of MOS and support its potential as a polymer-based dietary intervention for inflammatory bowel disease.