Objective  To explore the effect and mechanism of cycloastragenol (CAG) in the treatment of bronchopulmonary dysplasia (BPD) by inhibiting inflammatory response through network pharmacology combined with in vitro experiment.

Methods  Network pharmacology was used to screen and predict key targets and signaling pathways of CAG in treating BPD by regulating inflammatory response. The key targets obtained were molecular-docked and further verified by in vitro experiments to explore the possible mechanisms.

Results  Through network pharmacological analysis, 92 intersection targets of CAG, inflammation, and BPD were obtained. The protein-protein interaction (PPI) network showed that TNF, AKT1, NFKB1, STAT3, EGFR, HIF1A, TLR4, etc., may be the key targets of CAG in treating BPD. The results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the effects of CAG treatment on BPD were mainly through HIF-1, IL-17 and other signaling pathways. Molecular docking analysis showed that CAG had a high affinity to TNF, TLR4, and HIF1A. In the in vitro BPD cell model, quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed that mRNA levels of TNF-α, IL-1β, IL-6, IL-8, and IL-17A in the model group were significantly increased, while HIF-1α was significantly decreased, and TLR4 changes were not statistically significant. After CAG intervention, the expression of TNF-α and related inflammatory factors was significantly decreased, and the expression of HIF-1α was significantly increased. Meanwhile, Western Blot results also verified that CAG could effectively inhibit the level of TNF-α protein.

Conclusion  CAG may improve the inflammatory response of epithelial cells by inhibiting the expression of TNF-α and related inflammatory factors while increasing the expression of HIF-1α to alleviate BPD.

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