Chaihu-Jia-Longgu-Muli Decoction improves dizziness with anxiety in rats by modulating tryptophan metabolism.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Jia-Longgu-Muli Decoction (CLMD), recorded in Shang Han Za Bing Lun, has long been used in traditional Chinese medicine for dizziness, insomnia, epilepsy, anxiety, and depression. However, its mechanisms against dizziness with anxiety remain unclear. AIM OF THE STUDY: To validate a rat model of dizziness with anxiety induced by chronic restraint stress (CRS) combined with unilateral labyrinthectomy (UL), and to explore the potential mechanisms of CLMD intervention. MATERIALS AND METHODS: A rat model was established using chronic restraint stress (CRS) combined with unilateral labyrinthectomy (UL). Fifty Sprague-Dawley rats were divided into Control, Sham, Model, CLMD, and paroxetine (PLXT) groups. Behavioral tests assessed vestibular and anxiety-like behaviors. Serum CORT, ACTH, IL-1β, and IL-6 were measured by ELISA. GABAergic neurons, astrocytes, and macrophages in the vestibular nuclei were examined by immunohistochemistry and immunofluorescence. Serum metabolomics was analyzed using UPLC-Q-Orbitrap HRMS/MS. RESULTS: The Model group exhibited significant vestibular dysfunction and anxiety, with elevated inflammatory factors and stress hormones. CLMD intervention modulated inflammatory cytokines, stress hormones, GABAergic imbalance, and tryptophan-kynurenine metabolism. Twenty-nine differential metabolites were identified, mainly in tryptophan, phenylalanine/tyrosine, and fatty acid pathways. CONCLUSION: CLMD significantly promoted vestibular function recovery and alleviated anxiety symptoms by improving neuroplasticity, regulating metabolic pathways, and modulating inflammation, showing potential as a treatment for dizziness with anxiety.