Polysaccharides from Dicliptera chinensis (L.) Juss. Attenuates drug-induced liver injury by phosphorylating AMPK and thus facilitating the entry of FOXO3 into the cell nucleus

Background Isoniazid and rifampicin, frontline tuberculosis drugs, frequently induce drug-induced liver injury (DILI), marked by hepatitis and hepatocyte necrosis. Polysaccharides from Dicliptera chinensis (L.) Juss. (DCP) exhibit anti-inflammatory, antioxidant, and hepatoprotective properties, but their effects on DILI remain unexplored Objective This study investigated DCP therapeutic potential against DILI and elucidated its molecular mechanisms Methods In vivo (using C57BL/6 mice) and in vitro (using HepG2 cells) DILI models were established and treated with DCP. Transcriptomics, qRT-PCR, and Western blotting were employed to analyze pathway regulation Results DCP significantly attenuated hepatocyte apoptosis, inflammation, and oxidative stress in DILI mice. Transcriptomic analysis linked DCP'S effects to the modulation of AMPK-FOXO3, p53, and NF-κB pathways, alongside regulation of antioxidant and cell cycle genes. In HepG2 cells, DCP similarly protected against DILI by enhancing AMPK phosphorylation, which facilitated the FOXO3 nuclear translocation. Both models demonstrated DCP'S suppression of p53 and NF-κB activation, restoration of antioxidant defenses, and correction of cell cycle dysregulation Conclusion DCP mitigates DILI by reducing apoptosis, oxidative stress, and inflammation through activation of the AMPK-FOXO3 pathway, inhibition of p53/NF-κB signaling, and stabilization of the cell cycle. These findings highlight DCP'S potential as a therapeutic agent for DILI prevention and treatment