Analysis of Mechanism of Antidepressant Effect of Sophora flavescens Seed Extract / 中国实验方剂学杂志

ObjectiveTo explore the antidepressant effect of Sophora flavescens seed extract and its molecular mechanism. MethodA mouse depression model was established by intraperitoneal injection of lipopolysaccharide（LPS）， and normal group， model group， fluoxetine group（2.5 mg·kg-1）， and S. flavescens seed low， medium and high dose groups（200， 400， 800 mg·kg-1） were set up for 7 d of consecutive gavage. Then the antidepressant effect of S. flavescens seed extract was evaluated by using open field test， elevated plus maze test and forced swimming test. Pathological morphological changes in the hippocampal tissue was observed by hematoxylin-eosin（HE） staining. Protein expression levels of G1/S-specific cyclin D1（Cyclin D1）， Wnt1， β-catenin and phosphorylated glycogen synthase kinase-3β（p-GSK-3β） in mouse brain tissues were detected by Western blot. Hippocampal cell apoptosis was detected by terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate（dUTP） nick end labeling（TUNEL）. ResultThe results of mouse behavioral experiments showed that compared with the normal group， the speed of movement in the open field and the distance of movement in the central area of the open field， and the time spent on the open arms of the elevated plus maze were significantly reduced in the model group（P<0.01）， while immobility time in the forced swimming test was significantly increased（P<0.05）. Compared with the model group， the S. flavescens seed medium and high dose groups had increased speed of movement in the open field test and time spent on the open arms of the elevated plus maze test（P<0.05， P<0.01）， and decreased immobility time in the forced swimming test（P<0.05）， the distance of movement in the central area of the open field test increased in the high dose group（P<0.05）. HE staining results showed that compared with the normal group， the hippocampal neuron structure of mice in the model group was damaged. Compared with the model group， after treatment of S. flavescens seed extract， the pathological state of the mouse hippocampal neuron structure was alleviated， and the neurons increased， were neatly arranged， and the cytoplasm was clear. Western blot results showed that the protein expression levels of Wnt1 and β-catenin in mouse brain tissue were significantly decreased（P<0.01）， while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly increased（P<0.01） after LPS injection. Compared with the model group， protein expression levels of Wnt1 and β-catenin in brain tissue of S. flavescens seed medium and high dose groups were significantly increased（P<0.01）， while the protein expression levels of Cyclin D1 and p-GSK-3β were significantly decreased（P<0.01）. TUNEL staining results showed that the hippocampal cell apoptosis rate in the model group was significantly increased compared with that of the normal group（P<0.01）， while the hippocampal cell apoptosis rate in the S. flavescens seed medium and high dose groups was significantly decreased compared with that of the model group（P<0.01）. ConclusionS. flavescens seed extract can effectively improve the severity of depression in LPS-induced depressed mice， and its molecular mechanism is related to the regulation of neuroinflammation and hippocampal neuronal apoptosis mediated by Wnt/β-catenin signaling pathway.

Anxiolytic effect of antianxietic compound prescription capsule on acute stress in rats and influence upon expression of ERK/CREB signaling pathway and BDNF in the brain of rats / 中国药理学通报

Aim To study the pharmacodynamics of antianxietic compound prescription capsule ( ACPC ) on acute stress in rats and the influence upon the ex-pression of ERK/CREB signal pathway and brain-de-rived neurotrophic factor ( BDNF) in the cerebral cor-tex and hippocampus of rats. Methods The elevated plus maze ( EPM ) test was applied to observe the effects of ACPC on acute stress rats administered 7 d low-, medium- and high-dose ( 0. 75 , 1. 5 , 3 g · kg-1 ) . The expression of ERK/CREB signal pathway and BDNF in the cerebral cortex and hippocampus of rats were studied by using Western blot method. Re-sults In EPM, high-dose of ACPC increased signifi-cantly the rat open arm time ( OT%) ( P<0 . 05 ) and the percentage of open arm entries ( OE%) ( P <0. 05). In Western blot, the medium-dose of ACPC reduced significantly p-ERK1/2 expression in hippo-campus ( P <0. 05 ) , and high-dose group decreased significantly the expression of p-ERK1/2 and p-CREB in the cortex and hippocampus of rats ( P <0. 05 ) . High-dose group increased significantly the expression of BDNF in the cortex and hippocampus of rats ( P<0. 05 , P<0. 01 ) . Conclusion ACPC has anti-anxie-ty effect in the model of EPM, and its mechanism may be related to the ERK/CREB signal pathway and in-creased BDNF expression.

Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress / 中国中药杂志

Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like disorders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticosterone level, glucocorticoid receptor (GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12.5, 25, 50 mg x kg(-1)) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.

The mediation of immune activation on serotonin and glutamate systems in pathological process of depression / 中国药理学通报

Immunological alterations and changes in neurotransmission are considered to be crucial in the pathological process of depression. An immune activation including increased production of proinflammatory cytokines has repeatedly been described in depression, which shines a clue for new anti-depression therapy. Immune activation will lead to depression through serotonin and glutamate systems. This paper is attempted to review the immune mediated alterations on serotonin and glutamate systems.