Antidepressant‐like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus

Abstract

BACKGROUND AND PURPOSEGinsenoside Rg1 (Rg1) is one of the major bioactive ingredients of Panax ginseng with little toxicity and has been shown to have neuroprotective effects. In this study, we investigated the antidepressant-like effect of Rg1 in models of depression in mice. EXPERIMENTAL APPROACHThe effects of Rg1 were assessed in the forced swimming test (FST) and tail suspension test (TST) in mice. Rg1 was also investigated in the chronic mild stress (CMS) mouse model of depression with imipramine as the positive control. Changes in hippocampal neurogenesis and spine density, the brain-derived neurotrophic factor (BDNF) signalling pathway, and serum corticosterone level after chronic stress and Rg1 treatment were then investigated. The tryptophan hydroxylase inhibitor and the tyrosine kinase B inhibitor were also used to explore the antidepressive mechanisms of Rg1. KEY RESULTSGinsenoside Rg1 exhibited antidepressant-like activity in the FST and TST in mice without affecting locomotor activity. It was also effective in the CMS model of depression. Furthermore, Rg1 up-regulated the BDNF signalling pathway in the hippocampus and down-regulated serum corticosterone level during the CMS procedure. In addition, Rg1 was able to reverse the decrease in dendritic spine density and hippocampal neurogenesis caused by CMS. However, Rg1 had no discernable effect on the monoaminergic system. CONCLUSIONS AND IMPLICATIONSOur results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis.

Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine

“…Finally, the prevailing perception in the literature, suggests FST to be a proper test to show neurogenesis-dependence of antidepressant efficacy. Several groups described X-irradiation to block antidepressant effects using FST (e.g., Zhu et al, 2010;Garza et al, 2012) while correlative observations linking antidepressant treatment effects in FST and adult hippocampal neurogenesis have been reported numerous times (Liu et al, 2008;Silva et al, 2008;Schmidt and Duman, 2010;Wainwright et al, 2011;Wang et al, 2011;Jiang et al, 2012;Lin and Wang, 2014;Lu et al, 2014).…”

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

“…2,26) The mice were placed individually in the center of a wooden box (100×100×40 cm) with the floor divided into 25 (5×5 cm) squares and allowed to act at liberty. The apparatus was covered with a black surface and illuminated with a red bulb (50 W).…”

“…2,36) Thus, the possible antidepressant effects of AST were first examined in the FST. AST (10, 20, 40 mg/kg) was given i.p.…”

Neural Regeneration: Role of Traditional Chinese Medicine in Neurological Diseases Treatment

“…Jiang et al (30) reported the effect of Rg1 in a mouse model of chronic mild stress (CMS). Rg1 has antidepressant-like effect in the forced swim test and tail suspension test, and it could up-regulate the BDNF signaling pathway of the hippocampus and down-regulate the level of plasma corticosterone.…”