Harnessing Paeonia lactiflora-derived antioxidant carbon dots as oral nanomedicine for ulcerative colitis therapy by restoring intestinal mucosal barrier and microbiota homeostasis

The clinical management of ulcerative colitis (UC) necessitates the development of safe and efficacious oral therapeutic agents. Guided by network pharmacology predictions, this study successfully synthesized novel Paeonia lactiflora -derived carbon dots (PL-CDs) via a one-pot hydrothermal method using a single traditional Chinese medicine precursor. Physicochemical characterization and in vitro antioxidant assays demonstrated that PL-CDs possess robust, broad-spectrum radical scavenging capacity and SOD-mimetic antioxidant capacity. Cellular experiments revealed that PL-CDs were efficiently internalized by macrophages, subsequently reversing oxidative stress-induced mitochondrial dysfunction. Furthermore, PL-CDs orchestrated macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype and significantly reduced pro-inflammatory cytokine mRNA expression. In both preventive and therapeutic mouse models of dextran sulfate sodium (DSS)-induced colitis, oral administration of PL-CDs markedly reduced the disease activity index (DAI) and effectively mitigated intestinal histopathological damage. Mechanistic investigations further elucidated that PL-CDs not only repaired the compromised intestinal mucosal barrier by upregulating the expression of tight junction proteins but also effectively remodeled gut microbiota homeostasis. Collectively, this study highlights the comprehensive potential of PL-CDs in antioxidation, anti-inflammation, mucosal healing, and microbial regulation, offering a promising strategy for the development of TCM-derived oral nanomedicines for the treatment of ulcerative colitis.