The Antidepressant Effects and Mechanisms of Chuanxiong Volatile Oil on Chronic Unpredictable Mild Stress‐induced Mice

As life pressure mounts, depression cases surge. Conventional antidepressants have limited efficacy and notable side effects. Chuanxiong, a traditional Chinese medicine, orally benefits the nervous system. This study combines traditional aromatherapy with targeted therapy by utilizing small molecular volatile components that quickly enter the brain via the olfactory pathway to investigate the impact of inhaling Chuanxiong volatile oil on depressed mice. We identified the components of Chuanxiong volatile oil, predicted pathways and targets for its antidepressant effects, and elucidated mechanisms affecting hormone levels, the nervous system, and inflammatory responses. Depressed mice inhaling it regained normal weight, had longer open field activity time, more open arm entries in the elevated plus maze, and increased food intake. The detection of serum and brain tissue showed that inhaling Chuanxiong volatile oil effectively restored the levels of inflammatory factors such as interleukin (IL)-1β, IL-6, IL-10, and IL-18, and regulated the interaction between hypothalamic-pituitary-adrenal axis hormones, thereby alleviating the depressive-like symptoms in mice. Brain tissue staining showed that inhaling Chuanxiong volatile oil protected the nervous system. These findings indicate the feasibility of using Chuanxiong volatile oil to treat depression and provide a foundation for using aromatherapy to treat neurological diseases.