Anti-depressant effects of Jieyu Anshen granule in chronic unpredictable mild stress-treated rats after ischemic stroke / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule (JY) in chronic unpredictable mild stress (CUMS)-treated rats after ischemic stroke. METHODS A rat model of post-stroke depression(PSD)was developed by additional CUMS procedures after middle cere-bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg-1and 3 g·kg-1of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg-1)served as a reference drug.Behavioral tests including sucrose preference test, forced swim test and open-field test were performed to evaluate the antidepressant effects. Levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in rat brain were assayed. The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain. Serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were estimated as indices of hypothalamic-pituitary-adrenal (HPA) axis activity. Western blot analysis was used to evaluate hippo-campal expression of the 5-HT1A receptor (5-HT1AR) and brain-derived neurotrophic factor (BDNF). RESULTS PSD rats exhibited decreased sucrose consumption and motor activity, increased immobility time (P<0.01). JY treatment reversed the depressive behaviors in PSD rats (P<0.05, P<0.01). Treat-ment with JY resulted in significantly increased levels of NE, DA and 5-HT in the hippocampus and prefrontal cortex (P<0.05, P<0.01), and increased expression of 5- HT1AR and BDNF in the hippocampus(P<0.01). JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus andprefrontal cortex (P<0.05). Treatment with JY also resulted in significantly decreased ACTH and CORTin serum which had been increased (P<0.05). CONCLUSION These findings suggest that JY treat-ment could ameliorate PSD, and the effects are likely ascribed to inhibiting HPA axis hyperfunction andinflammatory, up-regulating the levels of neurotransmitters (NE, DA and 5-HT), and the expression ofhippocampal 5-HT1AR and BDNF.