IDDF2026-ABS-0209 Atractylodes macrocephala-derived carbon dot nanozymes for the multi-targeted treatment of ulcerative colitis: integrating antioxidant, anti-inflammatory, and gut barrier-protective effects

Background Current therapeutic agents for ulcerative colitis (UC) often face significant safety and efficacy limitations. To address these challenges, this study aimed to develop a novel carbon dot nanosystem (AM-CDs) derived from the traditional medicinal plant Atractylodes macrocephala. We investigated its potential to provide a multi-targeted therapy integrating antioxidant, anti-inflammatory, and intestinal barrier-restorative functions. Methods AM-CDs were synthesized via a green hydrothermal route and characterized using TEM, DLS, and XPS to determine their physicochemical properties. In vitro, the ROS scavenging and anti-inflammatory capacities of AM-CDs were evaluated in RAW264.7 macrophages using fluorescence probes and qPCR. In vivo, therapeutic efficacy was assessed in a DSS-induced colitis mouse model through the monitoring of body weight, colon length, inflammatory cytokines (TNF-α, IL-6), and tight junction proteins (ZO-1, occludin). Mechanistic insights were obtained through transcriptomic analysis focusing on the PI3K-Akt and Jak-STAT signaling pathways. Results AM-CDs presented as uniform nanoparticles (~5.0 nm) rich in hydrophilic groups (-OH, -COOH) (IDDF2026-ABS-0209 Figure 1. Preparation and characterization of AM-CDS). They demonstrated potent antioxidant activity, achieving >95% scavenging of hydroxyl radicals and superoxide anions (IDDF2026-ABS-0209 Figure 2. Evaluation of the antioxidative potential of AM-CDS). In vitro, AM-CDs were efficiently internalized by macrophages, significantly reducing intracellular ROS and downregulating pro-inflammatory cytokine expression (IDDF2026-ABS-0209 Figure 3. In vitro antioxidative and anti-inflammatory activities of AM-CDS). In vivo, AM-CD treatment significantly alleviated weight loss, colon shortening, and splenomegaly. Notably, AM-CDs restored mucosal integrity, increased mucus secretion, and upregulated tight junction protein expression, showing superior efficacy to conventional 5-ASA therapy (IDDF2026-ABS-0209 Figure 4. Evaluation of AM-CD efficacy in DSS colitis treatment). Mechanistically, these effects were mediated via the modulation of PI3K-Akt, Jak-STAT, TGF-β, and MAPK signaling pathways. No significant organ toxicity was observed (IDDF2026-ABS-0209 Figure 5. Mechanistic insights into the bioactivity of AM-CDS). Conclusions AM-CDs effectively ameliorate UC through a synergistic multi-targeted mechanism involving ROS scavenging, inflammation suppression, and barrier restoration. Given their superior performance compared to 5-ASA and excellent biosafety, AM-CDs represent a promising natural medicine-based nanotherapeutic platform for the precision treatment of inflammatory bowel disease.