Medicinal Plant-Derived Carbon Dots Nanozymes Ameliorate Ulcerative Colitis via Anti-inflammatory, Antioxidant, and Gut Barrier-Protective Effects

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by oxidative stress, immune dysregulation, and compromised intestinal barrier integrity. Current therapeutic agents are frequently limited by safety concerns. To address this clinical challenge, we pioneered the development of an innovative nanotherapeutic system derived from the medicinal plant Atractylodes macrocephala via hydrothermal synthesis, which integrates antioxidant, anti-inflammatory, and barrier-restorative functionalities. Comprehensive characterization demonstrated that A. macrocephala-derived carbon dots (AM-CDs) possess a uniform particle size (∼5.0 nm), abundant surface hydrophilic groups, and exhibit potent antioxidant activity by scavenging over 95% of hydroxyl radicals (^•OH) and superoxide anions (^•O₂^-). AM-CDs confer therapeutic benefits via a tripartite mechanism: potent antioxidant activity, characterized by the direct elimination of excessive intestinal reactive oxygen species (ROS), thereby disrupting the oxidative stress cascade; anti-inflammatory modulation, evidenced by the significant downregulation of key pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1β; and barrier reinforcement, demonstrated by enhanced secretion of mucin in the colonic mucus layer, restoration of intestinal epithelial tight junction proteins such as ZO-1 and occludin, and reduced infiltration of M1 macrophages and neutrophils. Mechanistic investigations revealed that these therapeutic benefits are mediated through coordinated regulation of critical signaling pathways, including PI3K-Akt, Jak-STAT, TGF-β, and MAPK, which synergistically orchestrate anti-inflammatory responses and barrier restoration. In conclusion, this study introduces an interdisciplinary approach termed "natural medicine-nanotechnology-multitarget modulation," which presents a multifunctional platform based on plant-derived carbon dots for the treatment of UC. The enhanced efficacy of AM-CDs, surpassing that of conventional 5-aminosalicylic acid (5-ASA) treatments, along with their favorable biosafety profile and potential for clinical translation, offers an innovative therapeutic strategy for the precise management of IBD.