Broussonin E against acute respiratory distress syndrome: the potential roles of anti-inflammatory.

We applied network pharmacology and molecular docking analyses to study the efficacy of Broussonin E (BRE) in acute respiratory distress syndrome (ARDS) treatment and to determine the core components, potential targets, and mechanism of action of BRE. The SwissTargetprediction and SEA databases were used to predict BRE targets, and the GeneCards and OMIM databases were used to predict ARDS-related genes. The drug targets and disease targets were mapped to obtain an intersecting drug target gene network, which was then uploaded into the String database for protein-protein interaction network analysis. The intersecting gene was also uploaded into the DAVID database for gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis. Molecular docking analysis was performed to verify the interaction of BRE with the key targets. Finally, to validate the experiment in vivo, we established an oleic acid-induced ARDS rat model and evaluated the protective effect of BRE on ARDS by histological evaluation and enzyme-linked immunosorbent assay. Overall, 79 targets of BRE and 3974 targets of ARDS were predicted, and 79 targets were obtained after intersection. Key genes such as HSP90AA1, JUN, ESR1, MTOR, and PIK3CA play important roles in the nucleus and cytoplasm by regulating the tumor necrosis factor, nuclear factor-κB, and PI3K-Akt signaling pathways. Molecular docking results showed that small molecules of BRE could freely bind to the active site of the target proteins. In vivo experiments showed that BRE could reduce ARDS-related histopathological changes, release of inflammatory factors, and infiltration of macrophages and oxidative stress reaction. BRE exerts its therapeutic effect on ARDS through target and multiple pathways. This study also predicted the potential mechanism of BRE on ARDS, which provides the theoretical basis for in-depth and comprehensive studies of BRE treatment on ARDS.