Ginsenoside Rh2 administration produces crucial antidepressant‐like effects in a CUMS‐induced mice model of depression

Abstract

Introduction The most striking feature of depression is sadness and a loss of interest in activities, which represents a major cause of disability globally. Therefore, it is necessary to identify novel antidepressants for clinical practice. Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides that can be extracted from Panax ginseng and has been demonstrated to improve both memory and learning. The purpose of this study was to provide broad insight into the mechanisms underlying depression and gain greater insights into antidepressant therapy. Methods In this study, we first established an effective and feasible depression animal model of chronic unpredictable mild stress (CUMS) and behavioral testing was evaluated by the forced swim test (FST), the tail suspension test (TST) and the sucrose preference test. Following pretreatment with Rh2 (10 and 20 mg/kg), the immobility time of mice was reduced without affecting locomotor activity in both the FST and TST. Western blotting and immunofluorescence were used to investigate the activation of the hippocampal BDNF signaling pathway and hippocampal neurogenesis. Results Different concentrations of Rh2 significantly reduced depressive‐like symptoms in CUMS‐induced mice and downregulated the effects of the BDNF signaling cascade and neurogenesis in the hippocampus. Furthermore, the administration of K252a completely prevented the antidepressant‐like activity of Rh2 in mice. Conclusion The results indicated that Rh2 possesses the antidepression action via the positive regulation of the BDNF‐TrkB pathway.

Suppressive effects of bilobalide on depression-like behaviors induced by chronic unpredictable mild stress in mice

“…One study showed that when a Trk-B antagonist was injected into mice exposed to CUMS it completely blocked the BDNF/Trk-B signaling cascade. 46 Regarding the neurotrophic hypothesis of depression, reduced expression of BDNF and other growth factors may contribute to mood disorders, while upregulation of BDNF and its receptor Trk-B may be a key component of the action of all antidepressants. 47…”

“…One study showed that when a Trk-B antagonist was injected into mice exposed to CUMS it completely blocked the BDNF/Trk-B sig-naling cascade. 46 Regarding the neurotrophic hypothesis of depression, reduced expression of BDNF and other growth factors may contribute to mood disorders, while upregulation of BDNF and its receptor Trk-B may be a key component of the action of all antidepressants. 47 Our study found that BDNF levels were significantly lower in the serum and brain tissue of CUMS-induced depressed mice compared to controls ( p < 0.01); however, both BB and fluoxetine ameliorated these changes to some extent (Fig.…”

Role of BDNF–TrkB signaling in the antidepressant‐like actions of loganin, the main active compound of Corni Fructus

“…Recent studies found that antidepressants enhanced neurotrophy by activating the downstream PI3K/Akt pathway of TrkB 48,49 . Moreover, numerous studies have shown that chronic stress attenuated neurogenesis, which some antidepressants were relieved via activating TrkB 50,51 . Furthermore, previous evidence shown that antidepressants inhibited neuroinflammation by activating TrkB to reduce the levels of NF‐κB, NLRP3, and pro‐inflammatory factors 52,53 .…”

“…# p < 0.05 and ## p < 0.01 compared with the CUMS group. some antidepressants were relieved via activating TrkB 50,51. Furthermore, previous evidence shown that antidepressants inhibited neuroinflammation by activating TrkB to reduce the levels of NF-κB, NLRP3, and pro-inflammatory factors 52,53.…”

Ginsenosides can target brain-derived neurotrophic factor to improve Parkinson's disease

“…134 Ginsenoside Rh2 and Rb1 exerts anti-depressant effects by positively regulating the BDNF-TrkB pathway. 135,136 Ginsenoside Rg1 increases the phosphorylation of BDNF, TrkB and Erk in the prefrontal cortex and improves learning, memory and adaptation by activating the BDNF/TrkB/Erk pathway in rats with CRS. 137 The mechanism by which ginsenosides improve PD is yet to be clarified.…”