From biomass side-product to nano-therapeutics: Characterization and anti-colitis efficacy of carbon dots originating from Nelumbinis Rhizomatis Nodus Carbonisatus

INTRODUCTION: Processing alters the efficacy of charcoal medicines, and derived carbon dots may be potential active components. This study prepared carbon dots from Nelumbinis Rhizomatis Nodus Carbonisatus (NRNCDs) to evaluate their therapeutic effects and mechanisms in ulcerative colitis (UC). METHODS: NRNCDs were isolated via aqueous extraction and dialysis and characterized by TEM and XPS. In vitro antioxidant activity was assessed using DPPH and ABTS assays. A DSS-induced mouse model was established to evaluate the effects of NRNCDs on disease activity index, colon length, histopathology, and inflammatory cytokines. RNA sequencing, RT-qPCR, and a S-adenosylmethionine (SAM) replenishment assay were used to elucidate the mechanisms. RESULTS: Monodisperse NRNCDs (2.25 ± 0.47 nm) with a carbon core and abundant oxygen and nitrogen surface groups were successfully fabricated, showing clear radical scavenging abilities. In vivo, NRNCDs significantly reduced disease activity index scores, alleviated colon shortening, and mitigated histopathological damage and colonic inflammation. Mechanistically, RNA-seq revealed that NRNCDs regulated the one-carbon metabolism pathway by suppressing the expression of the key gene Mat2a. Furthermore, exogenous SAM supplementation significantly reversed the protective effects of NRNCDs against UC. CONCLUSION: NRNCDs attenuate UC by regulating the Mat2a-SAM axis within the one-carbon metabolism pathway. These findings support carbon dots as an active substance basis of traditional charcoal medicines and suggest NRNCDs as a potential nanotherapeutic candidate for UC treatment.