This study demonstrates that an SDE-derived, volatile-rich formulation of Sihosogansan (SHSGS) produces rapid anxiolytic and antidepressant effects within 30 minutes when delivered intranasally. In zebrafish EEG and mouse behavioral models, intranasal SHSGS—unlike oral administration—consistently restored stress-related abnormalities.
Mechanistic analysis showed that SHSGS enhances GABAergic activity and BDNF/TrkB/ERK signaling, supporting fast neuroplastic changes.
Integrated chemical and network analyses further identified β-pinene, terpinen-4-ol, and α-terpineol as key Q-markers, providing a foundation for standardized development of rapid-acting herbal antidepressants.
Our study established a Corticosterone (CORT)-treated Primary Hippocampal Neuron (PHN) in vitro model to investigate stress-related hippocampal pathology while reducing the cost and time of animal experiments.
CORT exposure induced concentration-dependent neuronal damage, including increased ROS, loss of mitochondrial membrane potential, and impaired neurite growth and polarization. The model reproduced neurotrophic deficits observed in depression, showing reduced expression of BDNF, TrkB, and DCX. Fluoxetine (FLUX) reversed these CORT-induced impairments and restored neurotrophic signaling, supporting the model’s predictive validity.
This PHN-CORT system provides a practical platform for mechanistic studies of stress-induced neuronal dysfunction and early-stage screening of antidepressant candidates.
