Transcriptomic Analysis Reveals the Antioxidant and Anti-Inflammatory Mechanisms of EGCG-Zn Nanoparticles in Dextran Sulfate Sodium-Induced Colitis in Mice.

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent colonic inflammation, excessive oxidative stress, and impaired barrier function. Transition metal-based nanoparticles offer promising antioxidant platforms to address oxidative stress-related pathologies. To overcome the poor gastrointestinal stability of the potent dietary antioxidant epigallocatechin gallate (EGCG), we utilized zinc-coordinated EGCG (EGCG-Zn) nanoparticles (NPs), which function as a transition metal-phenolic network, to achieve sustained colonic release and overcome the poor gastrointestinal stability of free EGCG. The therapeutic efficacy and underlying mechanisms were evaluated in dextran sulfate sodium (DSS)-induced colitis in mice. Oral administration of EGCG-Zn NPs effectively reduced oxidative stress, suppressed pro-inflammatory cytokine production, alleviated colitis symptoms, and repaired the intestinal mucus and mechanical barriers. Mechanistically, transcriptomic analysis revealed that EGCG-Zn NPs pretreatment markedly reversed DSS-induced transcriptional alterations. Integrated K-means clustering and KEGG enrichment analyses further demonstrated that these protective effects were mediated by down-regulating inflammation-associated genes and up-regulating tight junction proteins, primarily involving the modulation of calcium signaling, T-cell differentiation, and the PI3K-Akt, Wnt, NF-κB, and TNF pathways. Collectively, these findings suggest that EGCG-Zn NPs alleviate DSS-induced colitis by mitigating inflammation, suppressing oxidative stress, and promoting epithelial barrier repair, supporting their potential as a functional nutraceutical for UC management.