Anxiolytic Effects of Acanthopanax senticosus-Schisandra chinensis Combination: Mechanistic Insights via HPA and Neuroinflammatory Modulation

Background: Anxiety disorders are highly prevalent and associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Acanthopanax senticosus (AS) and Schisandra chinensis (SC) individually exhibit anxiolytic properties, but the efficacy and mechanism of their combination remain unclear. Methods: The putative bioactive profile of the AS-SC combination was characterized. Its anxiolytic effects were evaluated in a rat model of conditioned fear-induced anxiety using behavioral tests, ELISA, and immunohistochemistry. Results: The AS-SC combination markedly alleviated anxiety-like behaviors, decreased circulating corticosterone and adrenocorticotropic hormone concentrations, suppressed the release of IL-1β, IL-6, and TNF-α, modulated hippocampal dopamine and serotonin levels, and reduced neuronal injury. Mechanistically, the combination decreased hypothalamic CRH expression and restored hippocampal glucocorticoid receptor (GR) balance. Conclusion: The AS-SC combination exerts anxiolytic effects primarily by restoring hippocampus-HPA axis negative feedback and suppressing neuroinflammation, highlighting its potential as a therapeutic strategy. Keywords: anxiety, conditioned fear, Acanthopanax senticosus-Schisandra chinensis , neuroinflammation, HPA axis negative feedback, glucocorticoid receptor