Objective: To explore the potential mechanism of complex rose-bergamot essential oil against anxiety accompanied with facial spots through network pharmacology.

Methods: The components of rose and bergamot essential oils were determined by GC-MS and obtained from literature, and their action targets were predicted by PubChem, SwissADME and SwissTargetPrediction databases. Using "Anxiety disorder" and "Facial pigmentation" as keywords, the relevant targets of anxiety disorder and facial spots were mined in the databases of DrugBank, TTD, GeneCards, and OMIM. The intersection targets of complex rose-bergamot essential oil and anxiety accompanied with facial spots diseases were obtained by making Venn diagram, respectively. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of intersection targets were carried out through STRING platform, Metascape, and KEGG Mapper databases. The "complex essential oil- component- target- pathway" network was constructed by Cytoscape software. The key active compounds and core targets were docked by AutoDock software.

Results: A total of 34 active components of complex rose-bergamot essential oil and 405 corresponding targets were obtained. The intersection targets of complex essential oil with anxiety disorder and facial spot were 88 and 34, respectively, and the related KEGG pathways were 137 and 123 items, respectively. Neroli acetate, Neroli alcohol, and Linalool in complex rose-bergamot essential oil could play a therapeutic role in anxiety disorder by regulating key targets such as SLC6A4, GRIN2B and DRD2 to participate in the neuroactive ligand-receptor interaction and serotonergic synapse and other pathways, they also could play a role in the treatment of facial spots by regulating key targets such as EGFR, VEGFA, and PIK3CA in the PI3K-AKT, JAK-STAT and other signal pathways. The molecular docking between the key compounds and the core targets showed that the binding energy was less than 0 kcal /mol, indicating that the compound and the target could bind stably.

Conclusion: Complex rose-bergamot essential oil can play a role in the treatment of anxiety disorder with facial spots through the synergistic mechanism of multicomponent, multitarget, and multipathway.