Objective To investigate the effect and mechanism of Chuanxiong (Chuanxiong Rhizoma) oil inhalation via nasal administration on chronic unpredictable mild stress (CUMS)-induced depressive mice. Methods The main components of Chuanxiong Rhizoma oil were identified by gas chromatography-mass spectrometry (GC-MS). A CUMS-induced depressive mouse model was established, and after drug intervention, the pharmacological effects of Chuanxiong Rhizoma oil were evaluated through behavioral tests, hematoxylin-eosin (HE) staining and Nissl staining. Mechanistic studies were conducted using ELISA, Western blotting, qRT-PCR and 16S rRNA. Results GC-MS identified Z-ligustilide and senkyunolide A as the primary components of Chuanxiong Rhizoma oil. Nasal inhalation of Chuanxiong Rhizoma oil significantly alleviated depressive-like behaviors in CUMS mice (P < 0.05, 0.01), reduced hippocampal neuronal damage, upregulated the expressions of brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB)/cAMP-response element binding protein (CREB) signaling pathway related proteins in hippocampus (P < 0.05, 0.01), elevated levels of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT) and norepinephrine (NE) (P < 0.05, 0.01), inhibited the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis (P < 0.05, 0.01), suppressed pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) in colon tissue (P < 0.05, 0.01), enhanced barrier function (P < 0.05, 0.01), and significantly ameliorated CUMS-induced gut microbiota dysbiosis. The CREB-specific inhibitor 666-15 significantly reversed the antidepressant effects of Chuanxiong Rhizoma oil (P < 0.01). Conclusion Nasal inhalation of Chuanxiong Rhizoma oil alleviates depression by improving gut dysfunction through BDNF/TrkB/CREB pathway.

depression  /  Chuanxiong Rhizoma oil  /  anti-inflammation  /  hypothalamic-pituitary-adrenal axis  /  gut microbiota  /  BDNF/TrkB/CREB pathway  /  Z-ligustilide  /  senkyunolide A