Carbon Dots Derived from Carbonized Citri Reticulatae Pericarpium (Chenpi) Alleviate Metabolic Dysfunction-Associated Steatohepatitis

Metabolic dysfunction-associated steatohepatitis (MASH) prevalence is rising globally, with approved targeted therapies associated with substantial adverse reactions. In this study, we synthesized carbon dots (CDs) derived from Citri Reticulatae Pericarpium (CRP-CDs) to investigate their safety and therapeutic effect against MASH. Here, novel CRP-CDs were synthesized via high-temperature carbonization and systematically characterized in terms of particle size, surface functional groups, and optical properties. We assessed the in vitro and in vivo biosafety of CRP-CDs. An FFA-induced fatty-degeneration HepG2 cell model was used to examine its regulation of hepatic lipid accumulation, while the HFD-induced mouse model was employed to evaluate its therapeutic efficacy against MASH. Data-independent acquisition mass spectrometry (DIA-MS) quantitative proteomics was performed to decipher its anti-MASH molecular mechanisms. The results showed that CRP-CDs displayed uniform particle size, abundant surface functional groups, and stable optical behaviors based on characterization tests. In vitro studies demonstrated that CRP-CDs exhibited excellent biocompatibility. CRP-CDs treatment effectively reduced intracellular TG and TC levels. Administration of CRP-CDs alleviated elevated serum biochemical parameters in HFD-induced MASH mice. Histological examination further revealed the protective effect of CRP-CDs on liver damage induced by HFD feeding. In addition, CRP-CDs decreased hepatic levels of IL-1β, IL-6, TNF-α, and MDA, and enhanced SOD activity as well as GSH content. Analysis of proteomic results demonstrated that CRP-CDs alleviated MASH pathogenesis via synergistic modulation of multiple signaling cascades rather than acting on a single pathway. Moreover, in vivo toxicity assessment validated the favorable systemic biosafety of CRP-CDs with no obvious adverse toxic effects in mice. In conclusion, novel CRP-CDs represent an environmentally friendly and biocompatible nanomaterial capable of effectively alleviating HFD-triggered MASH, which shows promise as a candidate for preclinical therapeutic development against fatty liver disease. Notably, these results are derived from preclinical short-term animal studies, and further validation is required prior to clinical translation.