Unveiling the mechanism of kaempferol in RSV-induced lung inflammation through metabolomics and network pharmacology

• Kaempferol reduced RSV-induced lung inflammation in mice. • Kaempferol improved the disorder of amino acid metabolism in RSV-infected mice. • Kaempferol alleviated lung inflammation caused by RSV infection through the JAK-STAT signaling pathway. Respiratory syncytial virus (RSV) is one of the leading pathogens associated with hospitalization for childhood pneumonia and is associated with substantial morbidity and fatality among young children and infants. There are no specific antiviral treatments for RSV infections. Kaempferol, a flavonoid present in traditional Chinese medicines, possesses antiviral activity and may affect RSV-induced lung inflammation; however, this relationship remains unclear. We employed network pharmacology to forecast the mechanism of kaempferol in the treatment of RSV pneumonia, and used gas chromatography-mass spectrometry (GC-MS) to examine the metabolic profiles in serum. We then integrated the analysis of differential metabolites with potential targets using MetScape and assessed the interactions between kaempferol and the key targets through molecular docking. Molecular biology experiments confirmed these predictions. Our results demonstrated that kaempferol alleviated RSV-induced lung inflammation, inhibited viral replication, and reduced lung damage, possibly by modulating the JAK-STAT signaling pathway. Kaempferol primarily alleviates metabolic disorders by targeting amino acid metabolism. Molecular docking analysis indicated a strong binding affinity of kaempferol for AKT1, CASP3, SRC, EGFR, STAT1, and IL-2. Kaempferol ameliorated the metabolic disruptions caused by RSV in the amino acid metabolism, via the JAK-STAT signaling cascade and mitigated the inflammatory response associated with RSV infection. This study not only provides foundational data for the broad application of kaempferol in anti-RSV research but also offers novel insights into the exploration of therapeutic mechanisms for RSV infections.