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
Zhaoxun Chen,Chen Zhao,Pengcheng Liu,Haohan Huang,Shuhong Zhang,Xiaoqing Wang
ObjectiveEmerging evidence has indicated that excessive reactive oxygen species (ROS) have detrimental effects on osteoarthritis (OA). This study aimed to elucidate the effects of melatonin (MT), an antioxidant indolamine secreted from the pineal gland, on chondrocyte senescence and cartilage degeneration, thereby clarifying the underlying mechanisms of ROS-induced OA pathogenesis.DesignHydrogen peroxide (H2O2) was used to induce oxidative stress in rat chondrocytes. ROS levels were evaluated using cytometry and immunofluorescence. Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay. Western blotting and qPCR (Quantiative Real-Time Polymerase Chain Reaction) were used to examine apoptosis and autophagy. For in vivo experiments, male Sprague-Dawley rats were randomly divided into a sham-operated group, DMM (destabilization of the medial meniscus) surgery group, and surgery groups that received melatonin. Knee joints were collected and stained for histological analysis.ResultsThe data demonstrated that melatonin treatment significantly suppressed H2O2-induced matrix degradation and apoptosis, and maintained mitochondrial redox homeostasis. In addition, an enhancement of autophagic flux was observed through western blotting. These findings corresponded with activation of the AMPK/Foxo3 signaling pathways upon melatonin treatment. Histological staining and transmission electron microscopy (TEM) micrographs also demonstrated that melatonin alleviated cartilage ossification and chondrocyte hypertrophy in vivo.ConclusionsOur results indicated that melatonin protected chondrocytes via mitochondrial redox homeostasis and autophagy. The effects of melatonin on senescence may apply to other age-related diseases. Thus, melatonin may have multiple potential therapeutic applications.
危险品化学品经营许可证（带存储）