Bioactive glycyrrhizic acid–astragalus polysaccharide hydrogel facilitates gastric ulcer healing via ROS scavenging and anti-apoptotic effects

Gastric ulcers are refractory wounds that pose a significant clinical challenge, underscoring the urgent need for effective and affordable therapeutic strategies. In this study, we purified a novel homogeneous astragalus polysaccharide (APS13) and elucidated its structure, which consists of a →4)-α-1,4-Glc(1→ backbone with glucose branches at the 6-position, as determined by 2D-NMR and glycosyl residue analysis. To enhance its tissue adhesion and drug release profile, APS13 was co-assembled with glycyrrhizic acid (GA) into a GA-APS hydrogel. The resulting hydrogel exhibited strong adhesion and prolonged gastric retention under acidic conditions. In vivo and in vitro studies demonstrated that the GA-APS hydrogel reduced ulcer area, improved mucosal integrity, and decreased apoptosis-related protein expression in a rat model of acute gastric ulcer. Comparative analyses showed enhanced therapeutic outcomes relative to treatment with GA or APS13 alone. Proteomic and cellular experiments further indicated that the hydrogel's protective effect is associated with attenuation of ROS-induced apoptosis. These findings highlight the therapeutic potential of APS13-based hydrogels and offer a natural-material strategy for addressing oxidative stress-related gastric injury.