A synergistic protective network of Polygonatum sibiricum-derived carbon nanoparticles against ethanol-induced and oxidative hepatic injury in HepG2 cells.

Liver disease remains a major global health burden. This study investigated the protective effects of Polygonatum sibiricum-derived carbon nanoparticles (PS-CNPs) against ethanol-induced and oxidative stress-mediated injury in HepG2 cells. The obtained PS-CNPs exhibited a uniform near-spherical morphology, amorphous carbon structure, and notable photoluminescence. PS-CNPs showed significant free radical-scavenging capacity against DPPH and reduced hydrogen peroxide (H₂O₂)-induced reactive oxygen species (ROS) generation in L929 cells in a concentration-dependent manner. Cytotoxicity assays indicated that PS-CNPs had low toxicity. Mechanistic studies revealed that PS-CNPs exerted hepatoprotective effects through a multi-level synergistic mechanism. The core of this mechanism contributed to the restoration of mitochondrial function by recovering Complex I activity, reducing ROS burst, and stabilizing the mitochondrial membrane potential. Consequently, PS-CNPs maintained cellular energy homeostasis and inhibited apoptosis. Furthermore, in alcoholic injury, PS-CNPs promoted ethanol metabolism (enhanced ADH activity) and maintained energy balance (restored LDH activity). In both injury models, they potently activated the endogenous antioxidant defense system (increased SOD and CAT activities, decreased MDA levels). These effects collectively formed a synergistic network extending from mitochondrial protection to overall cellular functional improvement, significantly reversing the decline in cell viability. In conclusion, this study demonstrated that PS-CNPs were a promising nanomaterial with multi-target protective potential. Their mechanism, centered on mitochondrial repair, synergistically enhanced detoxification, metabolic, and antioxidant functions, thereby providing a crucial theoretical foundation for the development of novel hepatoprotective agents.