Abstract
BackgroundBupleurum yinchowense Shan et Y. Li is widely used to treat depressive and anxiety disorders for hundreds of years in China. Total saikosaponins (TSS) is the major ingredient of Bupleurum yinchowense. A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and subsequent mammalian target of rapamycin (mTOR) signaling is responsible for synaptic maturation and may contribution to the synaptic alteration underlying depression. The aim of the study was to investigate the antidepressant-like and anxiolytic effect of TSS in chronic corticosterone-treated mice. The effect of TSS on synaptic proteins expression and AMPA receptor-mTOR signaling pathway alteration was also evaluated.MethodsDose-response effect of TSS (12.5, 25, 50 mg/kg) was investigated in forced swim test (FST) in ICR male mice. In the chronic corticosterine-treated model, TSS was given intragastrically once a day for 2 weeks and continued through the behavior testing period. Behavior tests and AMPA receptor related signaling pathway were investigated.ResultsTSS (25 and 50 mg/kg) decreased the immobility time in the FST when compared with the control group. TSS (25 mg/kg) showed antidepressant-like and anxiolytic effects in the chronic corticosterone treatment model in mice. TSS increased hippocampal synaptic proteins (synapsin-1 and postsynaptic density protein 95) expression. Immunohistochemistry analysis showed that TSS significantly increased the synapsin-1 expression in CA3 of hippocampus. TSS also increased hippocampal phosphorylation expression of GluR1 Ser 845 (AMPA receptor subunit) and its downstream regulators extracellular signaling-regulated kinase (ERK), protein kinase B (Akt) and mTOR.ConclusionTSS produces antidepressant-like and anxiolytic effects and increases synaptic proteins expression which may be mediated by induction of AMPA receptor and subsequent mTOR signaling pathway.
Highlights
Our preliminary experiments indicated that total saikosaponins (TSS) from Bupleurum yinchowense produced antidepressant-like effect in the forced swim test (FST), tail suspension test in normal mice
Total saikosaponins (TSS) produced antidepressant and anxiolytic effects in the chronic cortiocosterone-treated mice Open field test As shown in Fig. 3a, b, c, no significant difference in the distance moved and velocity was found between CORT
Our results showed that both TSS and citalopram exerted anxiolytic effect, as measured by a significant increase of time spent in the center of the open field and the increased percentage of open arm entries and percentage of time spent on the open arms in the Elevated plus maze (EPM) test, as well as by the decreased latency to feed in the Novelty suppressed feeding test (NSFT)
Summary
Li is widely used to treat depressive and anxiety disorders for hundreds of years in China. Total saikosaponins (TSS) is the major ingredient of Bupleurum yinchowense. A-amino-3hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and subsequent mammalian target of rapamycin (mTOR) signaling is responsible for synaptic maturation and may contribution to the synaptic alteration underlying depression. The aim of the study was to investigate the antidepressant-like and anxiolytic effect of TSS in chronic corticosterone-treated mice. The effect of TSS on synaptic proteins expression and AMPA receptor-mTOR signaling pathway alteration was evaluated. It was recorded that Bupleurum yinchowense has action of soothing liver and was used to treat depressive and mood related disorders [1]. Our preliminary experiments indicated that total saikosaponins (TSS) from Bupleurum yinchowense produced antidepressant-like effect in the forced swim test (FST), tail suspension test in normal mice. The underlying mechanisms of these effects are not yet clear
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