Ginseng-Derived Carbon Quantum Dots Enhance Systemic Exposure of Bioactive Ginsenosides and Amplify Energy Metabolism in Mice.

Objective: To overcome the extremely low oral bioavailability of ginsenosides in traditional ginseng preparations, this study aimed to evaluate the efficacy of a novel ginseng-derived carbon quantum dots (G-CQDs) delivery system and to elucidate its core bioactive constituents and integrated mechanisms of action. Methods: G-CQDs were prepared from ginseng roots via ultrahigh-speed nitrogen jet pulverization combined with far-infrared pulse-assisted hydrothermal carbonization. Their physicochemical properties were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and fluorescence spectroscopy. The in vivo effects of G-CQDs versus traditional ginseng aqueous extract (G-AE) were compared in C57BL/6 mice (n = 12/group) using the PRO-MRRM-8 Comprehensive Laboratory Animal Monitoring System for real-time, non-invasive phenotyping of energy metabolism parameters (respiratory quotient, heat production, and oxygen consumption). Systemic exposure to ginseng bioactives was profiled using UHPLC-Q/Orbitrap/LTQ high-resolution mass spectrometry, followed by bivariate correlation analysis to identify key bioactive components linked to efficacy. Results: Compared with G-AE, G-CQDs significantly enhanced whole-body energy metabolism-respiratory quotient +2.8%, heat production +6.7%, and locomotor activity +22.9% (p < 0.05). A total of 110 in vitro constituents, 35 blood prototypes, and 29 metabolites were identified. Correlation analysis revealed eight core bioactive clusters linked to the metabolic benefits; all showed higher systemic exposure with G-CQDs (range +9.2% to +265.8%), notably ginsenoside Re +69.6%, cinnamic acid + O + SO3 +157.4%, and linolenic acid-GSH conjugate +265.8%. Conclusions: Carbon quantum dot technology significantly enhances the systemic exposure of ginseng bioactivities by improving solubility and enhancing gastrointestinal absorption, providing a molecular basis for its superior efficacy in regulating energy metabolism compared to conventional extracts. This study establishes a novel framework for developing high-value, bioavailability-enhanced nano-preparations from traditional medicines.