Nanogel-encapsulated Rosa roxburghii Tratt fruit polyphenols ameliorated ulcerative colitis by regulating gut microbiota and PI3K/Akt and NF-κB pathways.

Rosa roxburghii Tratt fruit polyphenols (RP) possess antioxidant, anti-inflammatory, and immunomodulatory properties, showing potential for ulcerative colitis (UC) treatment. However, their efficacy is limited by bioavailability and targeting efficiency. To address this, RP were encapsulated into acylated chitosan-crosslinked carboxymethyl konjac glucomannan (ACs-CKGM) nanogel (RPNG). Experimental results demonstrated that RPNG significantly enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1, Occludin and Claudin-3) and mucus secretion (MUC2). It effectively mitigated oxidative stress by restoring antioxidant enzymes (SOD, GSH-Px and CAT) while reducing MPO, COX-2 and iNOS activation. Through integrated ELISA, western blot, and transcriptomic analyses, we emonstrated that RPNG specifically inhibited PI3K/Akt/mTOR and NF-κB signaling pathways, decreasing inflammatory cytokines (e.g., TNF-α, IL-6) while increasing anti-inflammatory mediators (e.g., IL-10). Gut microbiome analysis showed RPNG reversed DSS-induced dysbiosis by enriching beneficial bacteria (e.g., Muribaculum sp.) and suppressing pathogens (e.g., Escherichia coli). These findings highlight RPNG as a novel targeted strategy for UC management, supported by multi-omics mechanistic insights.