Objective This study aims to investigate the underlying mechanisms of Moutan Cortex (MC) against acute lung injury (ALI) by integrating network pharmacology, molecular docking and experimental validation in zebrafish and mice models. Methods UPLC-Q/TOF-MS was employed to characterize the phytochemical profile of MC. Potential pharmacological targets of MC and ALI were predicted using publicly available databases, followed by the construction of protein-protein interaction (PPI) networks and enrichment analyses based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Molecular docking was then performed to verify the binding affinity between key compounds and core target proteins. The protective effects of MC against ALI were further evaluated in lipopolysaccharide (LPS)-induced zebrafish and mice models. In zebrafish, the severity of swim bladder injury was examined using H&E staining, neutrophil recruitment imaging and qRT-PCR. In mice, histopathological changes and inflammatory mediators were assessed, while the expression levels of PI3K and Akt in lung tissues were determined by Western blotting and immunohistochemistry. Results Twenty-six compounds were identified from MC. Network pharmacological analysis highlighted ten core targets and implicated the PI3K/Akt as a key pathway. Molecular docking corroborated strong binding affinities between the principal compounds and core targets. Furthermore, MC markedly attenuated LPS-induced swim bladder injury, reduced neutrophil aggregation and downregulated the transcriptional levels of IL-6, TNF- α , PI3K and AKT1 in zebrafish. In an LPS-induced mice model of ALI, MC suppressed the secretion of proinflammatory cytokines and inhibited the phosphorylation of PI3K and Akt. Conclusion MC exerts protective effects against ALI partially through the modulation of the PI3K/Akt signaling pathway.
Guo et al. (Sat,) studied this question.