Dendrobium Officinale‐Derived Carbon Dots Nanozymes Alleviate Colitis by Orchestrating Intestinal Mucus‐Epithelium‐Immune Barriers

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder driven by genetic susceptibility, immune dysregulation, and intestinal barrier dysfunction. Current therapies primarily target immune suppression but show limited efficacy in barrier repair. Here, carbon dots derived from the Chinese herbal medicine Dendrobium officinale (DO-CDs), which exhibit antioxidant enzyme activity, are synthesized using a hydrothermal method. These DO-CDs, characterized by an abundance of surface functional groups, are demonstrated to scavenge ROS, suppress M1 macrophage polarization, as well as downregulate pro-inflammatory cytokine expression. In both acute and chronic colitis models, DO-CDs demonstrate multimodal barrier-repair properties. It is shown that DO-CDs can notably restore colon length, reduce the infiltration of inflammatory cells, and enhance both the quantity of goblet cells and the expression of mucins. Furthermore, the expression of intestinal epithelial tight junction proteins is significantly upregulated following DO-CDs treatment, thereby effectively strengthening the intestinal epithelial barrier function. Importantly, DO-CDs modulate the Th1/Treg ratio by downregulating the proportions of dendritic cells and M1 macrophages, thus reestablishing intestinal immune homeostasis. These coordinated actions on the mucus-epithelium-immune triad demonstrate the unique capacity of DO-CDs for holistic barrier reconstruction. The work provides a mechanistic foundation for herbal precursor-derived carbon dots as multi-target therapeutics in IBD.