Abstract
Treatment of the unpredictable chronic mild stress (UCMS) mice with the ethanol extract of Dipterocarpus alatus leaf attenuated anhedonia (increased sucrose preference) and behavioral despair (decreased immobility time in tail suspension test (TST) and forced swimming test (FST)). The extract not only decreased the elevation of serum corticosterone level and the index of over-activation of the hypothalamic-pituitary-adrenal (HPA) axis, caused by UCMS, but also ameliorated UCMS-induced up-regulation of serum- and glucocorticoid-inducible kinase 1 (SGK1) mRNA expression and down-regulation of cyclic AMP-responsive element binding (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in frontal cortex and hippocampus. In vitro monoamine oxidase (MAO) inhibition assays showed that the extract exhibited the partial selective inhibition on MAO-A. HPLC analysis of the extract showed the presence of flavonoids (luteolin-7-O-glucoside, kaempferol-3-glucoside, rutin) and phenolic acids (gallic acid, ferulic acid, and caffeic acid) as major constituents.
Highlights
Depression is one of the most debilitating and life-threatening mental disorders worldwide.Clinically, it is characterized by a loss of interest, depressed mood, anhedonia, guilty conscience, irritability, difficulty to concentrate, poor appetite, insomnia, and suicidal tendencies [1]
Imipramine (IMP)-treated unpredictable chronic mild stress (UCMS) mice showed a significant increase in 2% sucrose intake at the 5th week
The present findings demonstrated that the ethanol extract of D. alatus leaf ameliorated UCMS-induced depressant behaviors by reversing hyperactivation of the HPA axis and neurogenesis in the hippocampus and frontal cortex of UCMS mice
Summary
Depression is one of the most debilitating and life-threatening mental disorders worldwide. It is characterized by a loss of interest, depressed mood, anhedonia (reduced ability to feel pleasure from natural rewards), guilty conscience, irritability, difficulty to concentrate, poor appetite, insomnia, and suicidal tendencies [1]. Neurotransmission is involved in unpredictable chronic mild stress (UCMS)-induced depression-like behavior [2]. Excessive and prolonged chronic stress can impair the HPA axis negative feedback system, causing the hyperactivity and Molecules 2019, 24, 3396; doi:10.3390/molecules24183396 www.mdpi.com/journal/molecules. GCs, which are the most relevant biological factors in major depression disorder, regulate stress responses [4]. Solid evidences have shown that chronically high concentrations of GCs could impair hippocampal neurogenesis [5]
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