Scoparone protects against acetaminophen-induced acute liver injury: Insights from In vivo experiments and RNA sequencing

Background Scoparone (Sco) is known for its therapeutic effects in alleviating liver injury. This study aims to investigate the protective effects of Sco against acetaminophen-induced acute liver injury (ALI) and explore its underlying mechanisms through in vivo experiments and RNA sequencing. Methods Male Wistar rats were administered acetaminophen (400 mg/kg) to induce ALI, and Sco was given as an intervention. Liver injury and Sco's therapeutic efficacy were evaluated using histopathological analysis and biochemical indicators. RNA sequencing of liver tissue was performed to explore the molecular mechanisms, and differentially expressed genes were validated by qRT-PCR and in silico analysis. Results Histopathological analysis showed that Sco alleviated liver injury caused by acetaminophen. RNA sequencing identified 50 mRNAs and 93 lncRNAs whose expression was significantly altered by acetaminophen, with Sco reversing these changes. Gene enrichment analysis revealed that Sco counteracted alterations in genes involved in the Glycolysis/Gluconeogenesis pathway and the “external side of plasma membrane” GO term, which were induced by acetaminophen. Moreover, 17 lncRNA-mRNA pairs potentially associated with Sco-mediated liver protection were identified. qPCR validation confirmed the RNA sequencing results. In silico analysis suggested that TNFRSF1 4 might play a key role in the hepatoprotective mechanism, although this relationship requires further validation. Conclusions This study demonstrates that Scoparone effectively protects the liver from acetaminophen-induced injury. The results provide novel insights into the anti-inflammatory and antioxidative effects of Sco and suggest it as a potential therapeutic strategy for liver injury.