Antidepressant Activity of Astilbin: Involvement of Monoaminergic Neurotransmitters and BDNF Signal Pathway

Abstract

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that astilbin (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. In this study, the antidepressant-like effect of AST was investigated using chronic unpredictable mild stress ( Key words depression; astilbin; chronic unpredictable mild stress; serotonin; dopamine; brain-derived neurotrophic factor Depression is a serious medical illness that characterized by affective disorder. According to the World Health Organization (WHO), by the year 2030, depression will result in more years of life lost to disability than any other illness.1) At present, most antidepressants used clinically with low efficacy and many side effects can not meet the clinical needs. Therefore, with the increased prevalence of depression and social burden every year, the development of new antidepressants is becoming a top priority.Despite the fact that the molecular and cellular mechanisms remain unclear, a leading hypothesis of depression recently suggests that neurotrophic factors and adult neurogenesis play critical roles in mediating the behavioural responses to antidepressants.2) The brain-derived neurotrophic factor (BDNF) is closely related to neuronal survival and neurogenesis and plays an important role in animal models of depression. Various stress procedures including chronic unpredictable mild stress (CUMS) result in obviously decreases of BDNF expression in the brain, while chronic administration of almost all kinds of antidepressants including imipramine regulates BDNF levels. [3][4][5] The extracellular signal-regulated kinases (ERK) and AKT pathways are the two important downstream signaling pathways of BDNF. It has been reported that some of new antidepressants under development upregulate the expression of BDNF in different brain regions of stress mice via promoting the phosphorylation of ERK1/2 and AKT and thus activating the ERK, AKT pathways to produce antidepressant effects. [6][7][8] In recent studies, natural flavonoids especially resveratrol, tea polyphenols and curcumin show attractive prospect in the field of neural protection research.7,9,10) There is growing evidence indicated that flavonoids ameliorate the symptoms of depression via upregulating the levels of monoaminergic neurotransmitters 11) and promoting the expression of neurotrophic factors. 12,13)

Macranthol promotes hippocampal neuronal proliferation in mice via BDNF–TrkB–PI3K/Akt signaling pathway

“…In the present experiment, we focused our interest on the hippocampus, a crucial region involved in cognitive, memory and stress regulation (de Diego-Adelino et al, 2013;Boen et al, 2014), which was implicated in depression and antidepressant treatment. Our study provided evidence that chronic unpredictable mild stress caused a reduction in Akt phosphorylation in the hippocampus, which was in agreement with several previous studies Lv et al, 2014). Macranthol treatment significantly up-regulated the Akt phosphorylation.…”

Rapid identification of new minor chemical constituents from Smilacis Glabrae Rhizoma by combined use of UHPLC‐Q‐TOF‐MS, preparative HPLC and UHPLC‐SPE‐NMR‐MS techniques

“…It has been reported that flavonoids are the major bioactive components in this herb, for example, astilbin, a 3,5,7,3′,4′‐pentahydroxyflavanonol rhamnoside, is accepted as the marker component for quality control of Smilacis glabrae rhizome in China Pharmacopeia (Pharmacopoeia Commision of the PRC, ). It was reported to possess anti‐oxidation (Zhang et al ., ), anti‐inflammatory (Huang et al ., ), and anti‐depressant activities (Lv et al ., ). Besides, flavanol (e.g.…”

Effects of the total flavonoid extract of Xiaobuxin-Tang on depression-like behavior induced by lipopolysaccharide and proinflammatory cytokine levels in mice

“…It has been well documented that Hypericum perforatum, a "modern" herbal antidepressant, exerts extensive anti-inflammatory activities including the inhibitory activity on TNF-α, IL-1β, and LPS-induced prostaglandin E2 (Huang et al, 2011;Hammer and Birt, 2014). Recently, there is significant attention focused on the antidepressant-like effect of flavonoids extracted from herb medicines (González-Cortazar et al, 2013;Huerta-Reyes et al, 2013;Lv et al, 2014;Roohbakhsh et al, 2014;Reis et al, 2014), and it is notable that anti-inflammatory effect is also one of the primary biological activities of flavonoids (Tuñón et al, 2009;Shalini et al, 2012). Therefore, we may speculate that the anti-inflammatory effect of these herbs is possibly related to their antidepressant-like effect.…”