ReDuNing inhibits alveolar macrophage inflammation in LPS mice by activating JAK1/STAT3.

Background: The traditional Chinese medicine ReDuNing (RDN) is primarily composed of Artemisia annua , Gardenia jasminoides , Lonicera japonica , and clinically utilized for treating influenza. Therefore, we explored the mechanism of RDN in sepsis-induced lung injury.

Methods: Network pharmacology was used to identify the active components of RDN. A drug component network was constructed using Cytoscape 3.10.1 to identify key compounds, and a protein‒protein interaction (PPI) network was established using the STRING database. Common targets of RDN and sepsis were uploaded to the DAVID Bioinformatics Resources 6.8 for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to predict potential signaling pathways. In vitro, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays were used to detect the expression levels of JAK1/STAT3 and inflammatory factors. Subsequently, in vivo experiments were performed to validate these hypotheses.

Results: JAK1 was the most significantly enriched common target, and RDN may exert its effects via the JAK1/STAT3 signaling pathway. The expression of proinflammatory cytokines decreased in RDN-treated MH-S cells, which increased after inhibiting the JAK1/STAT3 pathway. The in vivo experimental results confirmed the in vitro findings.

Conclusion: RDN regulates the secretion of inflammatory cytokines by alveolar macrophages by activating the JAK1/STAT3 pathway, thereby alleviating sepsis-induced acute lung injury.