Exploration of Molecular Mechanisms and Potential Traditional Chinese Medicine Intervention in Acute Liver Injury

Objective This study aimed to explore the potential targets and molecular mechanisms underlying the progression of acute liver injury, as well as to predict traditional Chinese medicines associated with key targets. Methods Differentially expressed genes (DEGs) associated with acute liver injury were first screened. Then immune infiltration analysis was performed using CIBERSORT algorithm, followed by Weighted Gene Co-Expression Network Analysis (WGCNA) analysis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) analyses of overlapping genes between DEG and WGCNA were performed using the DAVID database. The main active components of the predicted Chinese medicines were determined through network pharmacology analysis. In vitro experiment was performed to observe the effects of different concentrations of quercetin on the inflammatory response of LPS-induced J774A.1 macrophages. Results The results showed elevated M1 macrophages and activated dendritic cells in acute liver injury. A total of 40 DEGs associated with M1 macrophages were obtained, which were significantly enriched in four pathways, including the Toll-like receptor signaling pathway ( P < .05). Furthermore, eight potential traditional Chinese medicines associated with Toll-like receptor signaling were identified, and network pharmacological analysis revealed quercetin as their main active ingredient. In vitro experimental results showed that quercetin reduced the mRNA levels of IL-6, TNF-α, IL-1β, and NF-κB as well as the protein levels of IL-6 and TNF-α in LPS-induced macrophages ( P < .05). Additionally, quercetin significantly inhibited the release of NO ( P < .05). Conclusion The present study provides further evidence that M1 macrophages potentially exert pro-inflammatory effects in acute liver injury via the toll-like receptor pathways. Notably, quercetin demonstrates inhibitory properties in this process, and its mechanism of action may be intricately linked to the TLR4-NF-κB signaling pathway.