Antidepressant Effect Of Astilbin:Involvement Of Monoaminergic Neurotransmitters And BDNF Signal Pathway

Background Depression is a serious medical illness with the increased prevalence. However, the classical antidepressants used clinically with narrow antidepressant spectrum and significant side effects can not meet the clinical needs. There is growing evidence indicated that natural flavonoids with high safety margins can significantly improve the symptoms of depression in recent years. Therefore, it provides a novel pharmacotherapy for the extraction and exploitation of natural flavonoids in the theatment of depression. Astilbin (AST), one of the natural flavonoids, is the main active constituents of many herbs, such as Rhizoma Smilacis Glabrae, Fructus Polygoni Orientalis, etc. Modern pharmacological researches indicate that AST has broad pharmacological functions which may modulate numerous pathways, such as antioxidant, scavenging free radicals, anti-inflammatory and so on, similarly to some of other flavonoids. As for the antidepressant effects of AST, it remains unclear.Objective The present study was to investigate the antidepressant-like effect of the natural flavonoid, AST on animal models and its corresponding mechanisms through the behavioral tests and molecular methods.Methods The male C57BL/6J mice were divided into control, model, Imipramine (10mg/kg), and different doses (10,20, and40mg/kg) of AST groups. The depressed mice model of chronic unpredictable mild stress (CUMS) was established for21d, during which the mice in different group were administered by ip once daily. The behavioral observations were conducted by measurement of forced swim test, tail suspension test and sucrose preference test. The contents of5-HT and DA and the expression of protein involved in brain-derived neurotrophic factor (BDNF) signal pathway in the prefrontal cortex were detected by HPLC and Western blot, respectively.Results AST treatment produces no effect on spontaneous locomotor activity of mice and the excitement of central nervous system. Compared with the control group, the immobility time of CUMS mice in the forced swim test and tail suspension test was markedly increased(P＜0.05); the sucrose preference, the contents of5-HT and DA, and the expression of BDNF, p-ERK and p-AKT in the prefrontal cortex were decreased(P＜0.05), and thus the depressed mice model was established successfully. Compared with the model group, chronic AST treatment could reverse the depressive-like behaviors of mice induced by CUMS(P<0.05), increase the concentrations of5-HT and DA(P<0.05), and up-regulate the expression of BDNF, p-ERK and p-AKT in the prefrontal cortex(P<0.05).Conclusion AST has antidepressant effects and the mechanisms may be related to up-regulation of5-HT and DA and activation of the BDNF signaling pathway.