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

Abstract

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.