title: Antidepressant-like effects of ginsenoside Rg1 are due to activation of the BDNF signalling pathway and neurogenesis in the hippocampus.
abstract: BACKGROUND AND PURPOSE Ginsenoside 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 APPROACH The 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 RESULTS Ginsenoside 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 IMPLICATIONS Our results provide the first evidence that Rg1 has antidepressant activity via activation of the BDNF signalling pathway and up-regulation of hippocampal neurogenesis.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Xiong
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhuang-Li
authors.initials: ZL
authors.lastname: Hu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Chen
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D013395:Sucrose / Q000008:administration & dosage; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D036145:Ginsenosides; D013395:Sucrose; C035054:ginsenoside Rg1; D003345:Corticosterone