Lavandula angustifolia essential oil attenuates chronic prostatitis by inhibiting PI3K/AKT and NF-κB signaling pathways.

Although lavandula angustifolia essential oil (LEO) has demonstrated anti-inflammatory properties, its mechanism in alleviating chronic prostatitis (CP) remains unclear. This study aimed to explore the pharmacological basis and molecular mechanisms of LEO's effect on CP. The chemical composition of LEO was analyzed using Gas Chromatography-Mass Spectrometry (GC-MS), identifying 15 active ingredients. A carrageenan-induced rat CP model was used to evaluate the impact of LEO on prostate index, inflammatory markers, and histopathological changes. The results showed that LEO significantly reduced the prostate index, inhibited inflammatory markers, and improved tissue damage. Multi-omics analysis, including transcriptome sequencing, Weighted Gene Co-expression Network Analysis (WGCNA), network pharmacology, and metabolomics, revealed that LEO modulates key pathways such as phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and nuclear factor kappa-B (NF-κB). Molecular distillation experiments and in vitro screening identified linalool and linalyl acetate as the main anti-inflammatory components of LEO. Molecular docking (MD) and molecular dynamics simulations (MDS) confirmed strong binding affinities of these compounds to AKT1 and Nuclear Factor Kappa B subunit P65 (P65), which were further validated by Surface Plasmon Resonance (SPR). Immunohistochemistry (IHC) and Western blot (WB) analyses confirmed the inhibition of cyclooxygenase-2 (COX-2), phosphatidylinositol 3-kinases (p-PI3K), phosphorylated protein kinase-B (p-AKT), and phosphorylated Nuclear Factor Kappa B subunit P65 (p-P65) expression. In conclusion, this study demonstrates that LEO alleviates CP through the PI3K/AKT/NF-κB pathway, primarily mediated by linalool and linalyl acetate, suggesting its potential as a therapeutic agent for CP.