Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop

Cherry leaves ( Prunus pseudocerasus Lindl. [Rosaceae] ), a traditional Chinese herbal medicine, can regulate the factors closely related to depression including inflammatory cytokines, oxidative stress and blood glucose level. However, the antidepressant effects of cherry leaves and underlying neuromodulatory mechanisms remain relatively have not been elucidated explicitly. The present study investigated the antidepressant effects of cherry leaf decoction (CLD). The underlying neuromodulatory mechanism was explored by examining the glutamate (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. The chronic unpredictable mild stress (CUMS) rodent model was used in this study. The main flavonoids components of CLD were identified using high-performance liquid chromatography (HPLC). The antidepressant effects of CLD were assessed throughout behavioural tests including the bodyweight, sucrose preference test (SPT), forced swimming test (FPT) and tail suspension test (TST). Moreover, The baseline levels of serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were quantified. The expression of proteins integrally involved in the Glu/GABA-Gln metabolic loop were observed and quantified by Western blotting, reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. This study found that CLD ameliorated depressive-like behaviours induced by CUMS. The increase of serum ACTH and CORT baseline levels induced by CUMS was also reversed after CLD intervention. Furthermore, CUMS reduced the expression of GAD65, GAD67, GLT-1, GS and GABA A and increased NMDAR1 levels in the rat hippocampus, which was normalized by CLD treatment. The findings demonstrated that CLD could ameliorate the depression-like behaviours induced by CUMS, potentially through the inhibition of hypothalamic–pituitary–adrenal (HPA) axis hyperactivity and the regulation of Glu/GABA-Gln metabolic loop. Graphical abstract