Herbal carbon dot nanozymes for integrated colitis therapy through ROS elimination, barrier restoration, and gut microbiota modulation

• Novel carbon nanodots derived from herbal Scutellaria baicalensis were synthesized for safe and biocompatible IBD treatment. • The ScuB-CDs exhibit cascade enzymatic activities (SOD/CAT) and potent free radical scavenging capacity. • In vitro studies demonstrate antioxidant, anti-inflammatory and intestinal barrier repair functions. • In vivo results show significant alleviation of DSS-induced IBD symptoms in mice. Inflammatory bowel disease (IBD) is an incurable and relapsing condition with rising global incidence. Long-term use of existing drugs often causes microbiota dysbiosis, excessive immunosuppression, and systemic toxicity. Although natural compounds like Scutellaria baicalensis , offer inherent anti-inflammatory and barrier-protective benefits with low toxicity, their poor water solubility and low bioavailability greatly limit clinical application. To address this challenge, a new class of Scutellaria baicalensis derived carbon dot nanozymes (ScuB-CDs) was designed. Capitalizing on both their unique carbon nanostructure and the retained bioactivity of their Scutellaria baicalensis precursor, the ScuB-CDs exhibited potent SOD-like and CAT-like activities, representing a dual-functional nanozyme system. In vitro , the ScuB-CDs significantly reduced H 2 O 2 -induced oxidative stress, upregulated tight junction proteins, and modulated macrophage polarization from M1 toward the M2 phenotype. In an IBD mouse model, oral administration of ScuB-CDs effectively alleviated inflammatory infiltration and pathological damage in colonic tissues, repaired the intestinal mucosal barrier, and restored the gut microbiota diversity. These findings demonstrate that the designed ScuB-CDs offer an integrated therapeutic strategy for colitis through ROS elimination, barrier restoration, and gut microbiota modulation.