Scutellaria Baicalensis‐Derived Carbon Dots Alleviate Colitis by Activating Anti‐Inflammatory and Barrier‐Protective Cascades

Ulcerative colitis (UC), a chronic inflammatory bowel disease, is hallmarked by persistent mucosal injury, oxidative stress, and dysregulated immune responses. Current therapies suffer from limited efficacy and systemic side effects, necessitating safer, targeted alternatives. Carbon dots (CDs) have emerged as versatile nanoplatforms, favored for their excellent biocompatibility and tailorable bioactivity. Inspired by the anti‐inflammatory and antioxidant properties of the traditional herb Scutellaria baicalensis, we developed herb‐derived CDs for targeted UC therapy. Three variants of CDs derived from Scutellaria baicalensis—namely, Carb‐CDs, Micro‐CDs, and Hydro‐CDs—were synthesized. Among these, Hydro‐CDs demonstrated superior performance, characterized by low cytotoxicity, strong reactive oxygen species (ROS) scavenging capabilities, enhanced superoxide dismutase (SOD)‐like activity, and improved anti‐inflammatory effects in macrophages. In the acute colitis model, Hydro‐CDs accumulated specifically in the inflamed colon tissues and markedly alleviated disease severity. Transcriptomic, KEGG, and Gene Set Enrichment Analysis (GSEA) analyses revealed Hydro‐CDs modulated critical signaling pathways (cAMP, calcium, and cGMP‐PKG), thereby reducing pro‐inflammatory cytokine secretion, upregulating tight junction protein expression, and restoring abnormal blood parameters. This study presents the inaugural synthesis of CDs derived from Scutellaria baicalensis and confirms their significant efficacy in UC treatment. It underscores the potential of herbal CDs as an innovative and synergistic nanotherapeutic approach for targeted intervention in inflammatory diseases, while also paving the way for the integration of natural medicinal components with nanotechnology.