Anshen Jieyu Decoction: A Promising Remedy for Depression via AKT/mTOR Pathway Modulation in CUMS Rats.

OBJECTIVE

To investigate the effects of An Shen Jie Yu Tang (ASJYD) on hippocampal morphology, AKT/mTOR phosphorylation, and serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in rats subjected to chronic unpredictable mild stress (CUMS).

METHODS

Three groups were used: Control, CUMS, and CUMS+ASJYD. Over 30 days, the CUMS and CUMS+ASJYD groups were exposed to stressors. After stress induction and behavioral assessments, the CUMS+ASJYD group received ASJYD for 14 days. Serum ACTH and CORT were quantified by ELISA. Hippocampal p-AKT/p-mTOR protein expression was evaluated by Western blot. Hippocampal neuron morphology was examined via Nissl staining, and mitochondrial ultrastructure via transmission electron microscopy.

RESULTS

Compared to controls, CUMS rats showed reduced sucrose preference, decreased distance/time in the open field center, and increased water maze latency (p<0.01). ASJYD ameliorated these impairments (p<0.01). CUMS rats exhibited elevated ACTH/CORT and decreased p-AKT/p-mTOR (p<0.01). ASJYD reduced ACTH/CORT and increased p-AKT/p-mTOR (p<0.01). Histology revealed CUMS rats had disorganized hippocampal neurons, reduced cell numbers, and nuclear abnormalities, which were improved by ASJYD.

CONCLUSIONS

ASJYD ameliorates CUMS-induced behavioral deficits, reduces hypothalamic-pituitary-adrenal axis hyperactivity, is associated with increased phosphorylation of AKT and mTOR, and protects against hippocampal neuronal damage.