Integrating GC-MS, network pharmacology, and molecular dynamics revealed the anti-insomnia mechanisms of brain-targeted ingredients in Artemisia argyi essential oil

Insomnia is a prevalent public health issue with limited safe and effective long-term treatments. Essential oils have demonstrated therapeutic potential in aromatherapy for insomnia, yet their active constituents and mechanisms remain largely unexplored. Artemisia argyi essential oil (AAEO) extracted from Artemisia argyi H.Lév. & Vaniot, a traditional Chinese medicinal herb , is particularly rich in bioactive terpenes . In this study, we systematically elucidated the brain-targeting ingredients and underlying anti-insomnia mechanisms of AAEO using an integrated experimental-computational approach. Aromatherapy with AAEO significantly increased cerebral levels of 5-HT and GABA in a PCPA-induced insomnia rat model (p < 0.05), confirming its insomnia therapeutic potential. Gas chromatography-mass spectrometry (GC-MS) identified 20 terpenes in AAEO, with monoterpenes and sesquiterpenes making up 89.6 % of the total content. Intranasal administration studies showed that 1,8-cineole and borneol are the primary brain-penetrant components. Network pharmacology analysis implicated that the serotonergic synapse pathway, especially via 5-HT1A, plays a key role in mediating AAEO’s anti-insomnia effects. Molecular docking and molecular dynamics simulations further demonstrated stable binding of both compounds to 5-HT1A, with 1,8-cineole exhibiting superior binding stability. These findings revealed a multi-component, brain-targeted mechanism underlying AAEO’s anti-insomnia activity and provide a molecular basis for the rational development of essential oil-based therapies for sleep disorders. • Identified brain-penetrant terpenes in AAEO, establishing a chemical basis for CNS efficacy of essential oil components. • Elucidating AAEO's anti-insomnia mechanism: multi-terpene synergy targets the 5-HT1A receptor. • A translational framework linking traditional AAEO use with mechanistic insights advances essential oil drug development.