Degradation Behavior and Mechanism of Agar Polysaccharides Induced by Hydrogen Peroxide: Structure Evolution and Bioactivity of Oligosaccharides.

Although H2O2-mediated degradation efficiently yields bioactive oligosaccharides, the underlying mechanisms and structure-activity relationships (SARs) of agar polysaccharides remain elusive. Here, the H2O2 degradation profiles of agar (FA) and agarose (TA) were systematically compared using HRMS/MS and 2D NMR. FA products underwent extensive hydrolytic ring-opening at 3,6-anhydro bridges, whereas TA products predominantly retained intact anhydro skeletons. In LPS-induced RAW 264.7 macrophages, intact TA oligosaccharides potently inhibited TNF-α and IL-6 secretion, whereas ring-opened FA oligosaccharides lost anti-inflammatory activity and triggered pro-inflammatory responses. This study elucidates the specific SAR of agar polysaccharides and identifies 3,6-anhydro-l-galactose as the essential anti-inflammatory pharmacophore, offering a robust theoretical basis for the targeted green preparation of bioactive marine oligosaccharides.