Research reportAntidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression

•Ginsenoside Rg2 possesses antidepressant effects in the FST and TST.•Ginsenoside Rg2 has antidepressant effects in the CMS model of depression.•Ginsenoside Rg2 has promoting effects on BDNF system in the hippocampus.

Major depression is a common neuropsychiatric disease with high lifetime prevalence and high incidence of suicide. This study aimed to evaluate the antidepressant effects of ginsenoside Rg2 in mice, and the possible mechanism was also determined. A single injection of both Rg2 (10 and 20 mg/kg) and fluoxetine (positive control, 20 mg/kg) induced notable antidepressant-like effects in the forced swim test and tail suspension test without affecting the locomotor activity of mice, and the tests were done 30 min after the injection. Also, repeated daily treatment of Rg2 and fluoxetine for the last 2 weeks fully reversed the chronic mild stress (6 weeks)-induced depressive-like symptoms in mice. Moreover, western blot analysis showed that Rg2 administration significantly increased the BDNF signaling pathway in hippocampus. Importantly, the usage of TrkB shRNA fully blocked the antidepressant effects of Rg2 in mice. Collectively, these results suggest that Rg2 produces an antidepressant-like effect in mice which is mediated, at least in part, through promoting the hippocampal BDNF signaling pathway.