Potential roles of inhalation aromatherapy on stress-induced depression by inhibiting inflammation in the peripheral olfactory system.

According to principles of Traditional Chinese Medicine, the nose is the passage for exogenous evil to invade the body, while essential or volatile oils extracted from herbs have the effects of dispelling melancholy, repelling foulness, and resuscitation with aromatics. Inhalation aromatherapy can target the brain and has a potential therapeutic effect on mood disorders. However, in particular, the mechanism of the effect of inhalation aromatherapy on the olfactory mucosa (OM) of the nasal cavity at the peripheral level, the first step in olfactory detection, where olfactory sensory neurons (OSNs) relay information to brain for signal processing, remains unclear. Here, we examined the roles of inhalation aromatherapy with compound essential oils derived from Bergamot, Peppermint and Rosa rugose on chronic unpredictable mild stress (CUMS)-induced depression and explored potential therapeutic targets in the peripheral OM. We found that inhalation aromatherapy effectively ameliorated CUMS-induced depression and olfactory dysfunction in rats. Strikingly, inhalation aromatherapy improved pathological changes, significantly reduced apoptosis levels, and promoted olfactory neurogenesis in the OM, which may contribute to the beneficial effects on the olfactory function of depressed rats. Further, inhalation aromatherapy significantly may reverse inflammation levels in the OM through Sirt1/FKBP5/GR/NF-κB signaling pathway, and prevented neuroinflammation in other parts of the olfactory system such as the hippocampus and prefrontal cortex, which may play a role in the olfactory impairments in rats with depression. Collectively, we have demonstrated that inhalation aromatherapy could efficiently prevent the local inflammatory responses in the OM of CUMS depression model rats. These findings provide new insights into the treatment of depression with aromatherapy, as well as new concept for the identification of novel antidepressant strategies.