Depression is a serious
psychiatric disorder with high prevalence, and the delayed onset of
antidepressant effects remains a limitation in the treatment of depression. This study aimed to screen
essential oils that have the potential for rapid-acting
antidepressant development. PC12 and BV2 cells were used to identify
essential oils with
neuroprotective effects at doses of 0.1 and 1 µg/mL. The resulting candidates were treated intranasally (25 mg/kg) to ICR mice, followed by a tail suspension test (TST) and an elevated plus maze (EPM) after 30 min. In each effective
essential oil, five main compounds were computationally analyzed, targeting
glutamate receptor subunits. As a result, 19
essential oils significantly abolished
corticosterone (CORT)-induced cell death and
lactate dehydrogenase (LDH) leakage, and 13 reduced
lipopolysaccharide (LPS)-induced
tumor necrosis factor alpha (TNF-α) and
interleukin 6 (IL-6). From in vivo experiments, six
essential oils decreased the immobility time of mice in the TST, in which Chrysanthemum morifolium Ramat. and Myristica fragrans Houtt. also increased time and entries into the open arms of the EPM. Four compounds including
atractylon, α-curcumene, α-
farnesene, and selina-4(14),7(11)-dien-8-one had an affinity toward GluN1, GluN2B, and Glu2A receptor subunits surpassed that of the reference compound
ketamine. Overall, Atractylodes lancea (Thunb.) DC and Chrysanthemum morifolium Ramat
essential oils are worthy of further research for fast-acting
antidepressants through interactions with
glutamate receptors, and their main compounds (atractylon, α-curcumene, α-farnesene, and selina-4(14),7(11)-dien-8-one) are predicted to underlie the fast-acting effect.