Fatty Acids Derived from Royal Jelly Exert Anti-Inflammatory and Antibacterial Activities in the Treatment of <i>Pseudomonas aeruginosa</i> -Induced Acute Pneumonia

<i>Pseudomonas aeruginosa</i>, an opportunistic pathogen, commonly causes hospital-acquired pneumonia. Royal jelly fatty acids (RJFAs), a mixture of various fatty acids extracted from royal jelly, exhibit antibacterial and anti-inflammatory properties in treating many infectious diseases. Nevertheless, the therapeutic mechanisms of RJFAs in treatment of acute <i>P. aeruginosa</i> pulmonary infection are still unclear. Herein, we initially extracted the fatty acids from royal jelly and characterized their chemical constituents using headspace gas chromatography-mass spectrometry. Furthermore, we examined the antibacterial effect of RJFAs <i>in vitro</i> and explored its therapeutic effect and molecular mechanisms in treating acute <i>P. aeruginosa</i> pulmonary infection <i>in vivo</i>. The <i>in vitro</i> antibacterial studies revealed that RJFAs significantly inhibited <i>P. aeruginosa</i> growth. Moreover, the <i>in vivo</i> studies showed that the RJFAs effectively mitigated the lung damage and inflammation induced by <i>P. aeruginosa</i> through impairing neutrophil infiltration, reducing the bacterial load in lung and diminishing the production of proinflammatory cytokines, including tumor necrosis factor (TNF-α), interleukin (IL-1β), IL-6, and macrophage inflammatory protein-2 (MIP-2). In addition, the mice treated with RJFAs exhibited reduced phosphorylation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK), c-Jun, and nuclear factor-kappa B (NF-κB) p65 in the lung tissues in comparison with that of the mice without drug treatment. These findings demonstrated that RJFAs exhibited significant antibacterial and anti-inflammatory effects in treating the <i>P. aeruginosa</i>-induced acute pneumonia, and the anti-inflammatory effects were exerted through suppressing the mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and NF-κB activation, suggesting a promising therapeutic potential of RJFAs against acute bacterial pneumonia.