Abstract

Gallic acid (GA), recognized for its antioxidant and anti-inflammatory bioactivities, has demonstrated efficacy in ameliorating experimental colitis. However, its clinical translation is impeded by poor water solubility. Deep eutectic solvents (DESs), as environmentally friendly green solvent systems, have emerged as promising candidates to address this limitation. Hydrogels are considered a viable strategy to enhance the anti-colitis efficacy of GA. The hydrogel (PC-CuGA) was fabricated using a one-step mixing method and cross-linked through non-covalent interactions by DES, polyvinyl alcohol (PVA), chitosan (CS), GA, and Cu 2 + . Additionally, DSS-evoked colitis was established and applied to clarify the regulatory efficacy of PC-CuGA on intestinal barrier impairment, inflammatory response, and redox imbalance. Results revealed that PC-CuGA exhibited a robust gel state with excellent temporal stability, superior storage modulus, enhanced structural integrity, and favorable biosafety. In the colitis model, PC-CuGA intervention effectively mitigated DSS-induced pathology, as evidenced by reduced weight loss, attenuated colon shortening, and lowered disease activity index (DAI) scores. Histopathological analysis further demonstrated that PC-CuGA preserved intestinal barrier integrity and protected tight junction proteins. Mechanistically, PC-CuGA significantly dampened the activation of the TLR4/MyD88/NF-κB axis and downregulated the expression of pro-inflammatory cytokine genes, while upregulating the expression of anti-inflammatory cytokines. Collectively, these findings elucidate that the protective effects of PC-CuGA against experimental colitis associated with reinforcing intestinal barriers, suppressing oxidative stress, and excessive inflammation. This work provides a novel therapeutic strategy for the prevention and management of colitis, highlighting the pote