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

다국어 초록 (Multilingual Abstract)

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