Journal of Natural Medicines

, Volume 71, Issue 2, pp 367–379 | Cite as

Antidepressant-like effects of ginsenoside Rg3 in mice via activation of the hippocampal BDNF signaling cascade

  • Zhengchen YouEmail author
  • Qi Yao
  • Jianhong Shen
  • Zhikai Gu
  • Hui Xu
  • Zhonghua Wu
  • Chuanjun Chen
  • Luozhu Li
Original Paper


Current antidepressants are clinically effective only after several weeks of administration. Ginsenoside Rg3 is one component of ginsenosides, with a similar chemical structure to ginsenoside Rg1. Here, we investigated the antidepressant effects of Rg3 in mouse models of depression. The antidepressant actions of Rg3 were first examined in the forced swim test (FST) and tail suspension test (TST), and then assessed in the chronic social defeat stress (CSDS) model of depression. The changes in the hippocampal brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and Rg3 treatment were investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of Rg3. It was found that Rg3 produced antidepressant effects in the FST and TST without affecting locomotor activity. Rg3 also prevented the CSDS-induced depressive-like symptoms. Moreover, Rg3 fully restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway, and use of the BDNF signaling inhibitor blocked the antidepressant effects of Rg3. In conclusion, ginsenoside Rg3 has antidepressant effects via promotion of the hippocampal BDNF signaling pathway.


Brain-derived neurotrophic factor Chronic social defeat stress Depression Ginsenoside Rg3 



AMP-activated protein kinase


Analysis of variance


Brain-derived neurotrophic factor


cAMP response element-binding protein


Chronic social defeat stress


Forced swimming test


Monoamine oxidase inhibitor


Noradrenergic reuptake inhibitor


p-Chlorophenylalanine methyl ester


Phosphoinositide 3-kinase


Serotonin–noradrenaline reuptake inhibitor


Selective serotonin reuptake inhibitor


Tricyclic antidepressant


Tropomyosin receptor kinase B


Tail suspension test



This work was funded by innovation and demonstration projects of Nantong Social Science and Technology (HS2011024) to Jianhong Shen.

Compliance with ethical standards

Conflict of interest

The authors have no conflicts of interest to report.


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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Zhengchen You
    • 1
    Email author
  • Qi Yao
    • 2
  • Jianhong Shen
    • 2
  • Zhikai Gu
    • 2
  • Hui Xu
    • 3
  • Zhonghua Wu
    • 3
  • Chuanjun Chen
    • 1
  • Luozhu Li
    • 1
  1. 1.Department of Burns and Plastic Surgery, Taizhou People’s HospitalThe Fifth Affiliated Hospital of Medical College of Nantong UniversityTaizhouChina
  2. 2.Department of NeurosurgeryAffiliated Hospital of Nantong UniversityNantongChina
  3. 3.Department of NeurosurgeryThe Sixth People’s Hospital of NantongNantongChina

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