Ginsenoside Rb1 Produces Antidepressant-Like Effects in a Chronic Social Defeat Stress Model of Depression Through the BDNF–Trkb Signaling Pathway

Ning Jiang,Yiwen Zhang,Qinghu He,Xinmin Liu,Qiong Wang,Jingwei Lv,Hong Huang

doi:10.3389/fphar.2021.680903

Abstract

Ginsenoside Rb1 (Rb1), an important bioactive ingredient of Panax ginseng, has potent neuroprotective effects. The objective of the study is to elucidate the impact of Rb1 treatment on chronic social defeat stress (CSDS)–induced depressive-like behaviors and its related mechanism. According to the obtained results, the daily oral administration of Rb1 (35 and 70 mg/kg) and imipramine (15 mg/kg) for 28 days significantly reversed the social avoidance behavior, anhedonia, and behavioral despair via CSDS exposure, as demonstrated by the considerable elevation in the time in the zone in the social interaction test, consumption of sucrose solution in the sucrose preference test, and decrease in immobility time in the forced swim test. Moreover, Rb1 obviously restored the CSDS-induced decrease in the BDNF signaling pathway and hippocampal neurogenesis. Rb1 significantly increased the hippocampal levels of ERK, AKT, and CREB phosphorylation and increased the number of DCX+ cells in DG. Importantly, the antidepressant effects of Rb1 were completely blocked in mice by using K252a (the nonselective tyrosine kinase B inhibitor). In conclusion, our results indicated that Rb1 exerts promising antidepressant-like effects in mice with CSDS-induced depression, and its effects were facilitated by enhancing the BDNF signaling cascade and upregulation of hippocampal neurogenesis.

Highlights

Stress is substantially involved in many neuropsychiatric complications, such as anxiety, depression, and posttraumatic stress disorders
After 28 consecutive days of modeling and drug administration, different depressive-like behaviors were evaluated. These behaviors included anhedonia, as assessed by the sucrose preference test (SPT); social avoidance, as measured by the time spent in the interaction zone (IZ); and behavioral despair, as evidenced by the immobility time in the forced swim test (FST)
In the vehicle-treated chronic social defeat stress (CSDS)-exposed group, significant declines in the time spent in the IZ and social interaction (SI) ratio in the SIT (F4,45 5.903, p < 0.01; F4,45 6.500, p < 0.01) and sucrose consumption (F4,45 31.747, p < 0.01) and an increase in the immobility time in the FST (F4,45 6.109, p < 0.01) were observed, as shown in Figures 2A–E, respectively

Summary

Introduction

Stress is substantially involved in many neuropsychiatric complications, such as anxiety, depression, and posttraumatic stress disorders. Depression is a prevalent neuropsychiatric disorder, and its main clinical characteristics are constant and obvious depression of mood. The lifetime prevalence of depression is approximately 15–20%, which means that almost one in five people experience depression in their lifetime, and 15% of cases of major depressive disorder result in suicidal deaths (Malhi and Mann, 2018). During the last few years, the monoamine hypothesis has been one of the most widely studied etiologies of depression. Most currently used antidepressants work by increasing the levels of monoamine. These antidepressant agents usually take weeks to months to exert their therapeutic effects. There is a need to develop more effective and safer antidepressants

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