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.

Atractylodes lancea (Thunb.) DC. (AL) has been indicated in traditional prescriptions for the treatment of depression. However, the mechanism of action of AL in the treatment of depression is still unclear. This study aimed to investigate the antidepressant potential of AL using network pharmacology, molecular docking, and animal experiments. The active components of AL were retrieved from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), and the depression-related targets were screened through the DisGeNET database. Overlapping targets of AL and depression were selected and analyzed. Ten active compounds of AL showed anti-depressant potential, including stigmasterol, 3β-acetoxyatractylone, wogonin, β-sitosterol, selina-4(14),7(11)-dien-8-one, atractylenolide I, atractylenolide II, atractylenolide III, patchoulene, and cyperene. These compounds target 28 potential antidepressant genes/proteins. Gene Ontology (GO) enrichment analysis revealed that the potential targets might directly influence neural cells and regulate neuroinflammation and neurotransmitter-related processes. The potential Kyoto Encyclopedia Genes and Genomes (KEGG) pathways for the antidepressant effects of AL include neuroactive ligand–receptor interactions, calcium signaling pathways, dopaminergic synapse, interleukin (IL)-17 signaling pathways, and the pathways of neurodegeneration. IL-6, nitric oxide synthase 3 (NOS), solute carrier family 6 member 4 (SLC6A4), estrogen receptor (ESR1), and tumor necrosis factor (TNF) were the most important proteins in the protein–protein interaction network and these proteins showed high binding affinities with the corresponding AL compounds. AL showed an antidepressant effect in mice by decreasing immobility time in the tail suspension test and increasing the total contact number in the social interaction test. This study demonstrated the antidepressant potential of AL, which provides evidence for pursuing further studies to develop a novel antidepressant.

Aromatherapy is one of the most common safer alternative treatments for psychiatric disorders with fewer side effects than conventional drugs. Here, we investigated the effects of cinnamon essential oil (CIEO) inhalation on mouse behaviors by performing different behavioral tests. CIEO inhalation showed anxiolytic effects in the elevated plus maze test, as inferred from increased time spent in open arms and decreased time spent in closed arms. Moreover, the CIEO treatment enhanced social behavior by increasing the total contact number, time spent in the center, distance traveled in the center, and total distance in the social interaction test. However, CIEO inhalation did not have any effect on performance in the open field test, tail suspension test, forced swimming test, and Y maze tests. The microarray analysis indicated that the CIEO treatment downregulated 17 genes and upregulated 15 genes in the hippocampus. Among them, Dcc, Egr2, and Fos are the most crucial genes that are involved in anxiety-related biological processes and pathways, including the regulation of neuronal death and neuroinflammation. Gas chromatography/mass spectrometry analysis revealed that cinnamaldehyde is the main component of CIEO. Cinnamaldehyde recovered MK-801-induced anxiety-related changes in the electroencephalogram power spectrum in zebrafish. Taken together, our findings suggest that CIEO and its main component cinnamaldehyde have an anxiolytic effect through the regulation of the expression of genes related to neuroinflammatory response and neuronal death.

Appetite dysregulation is one of the factors contributing to anorexia, bulimia nervosa, obesity, and diabetes. Essential oils or fragrant compounds have been proven to regulate food intake and energy expenditure; hence, this study aimed to summarize their effects on appetite and the underlying mechanisms. The PubMed and Web of Science databases were searched until July 2022. Only two of the 41 studies were performed clinically, and the remaining 39 used animal models. Oral administration was the most common route, and a dosage range of 100–2000 mg/kg for mice or 2–32 mg/kg for rats was applied, with a duration of 12 days to 4 weeks, followed by inhalation (10−6–10−3 mg/cage or 10−9–10−2 mg/cm3 within 1 h). Approximately 11 essential oil samples and 22 fragrant compounds were found to increase appetite, while 12 essential oils and seven compounds decreased appetite. These fragrant components can exert appetite-regulating effects via leptin resistance, the activity of sympathetic/parasympathetic nerves, or the mRNA expression of neuropeptide Y (NPY)/agouti-related protein (AgRP), cocaine- and amphetamine-regulated transcript (CART)/proopiomelanocortin (POMC) in the hypothalamus. Fragrance memory and cognitive processes may also play roles in appetite regulation. The findings of this study accentuate the potential of essential oils and fragrant compounds to regulate appetite and eating disorders.