Abstract
Panax ginseng C.A. Meyer (Araliaceae), a popular tonic and dietetic herbal medicine, has been traditionally prescribed in China and other countries to treat affective disorders. The medicinal parts of ginseng, the roots and flower buds, have become increasingly popular as dietary supplements due to the current holistic healthcare trend. We have investigated for the first time the antidepressive actions of the different medicinal parts, namely, the main roots, fibrous roots, and flower buds (in water extract and powder), of garden-cultivated ginseng through behavioral and drug-induced tests in mice. The water extracts, but not the powders of ginseng fibrous roots, flower buds, and main roots (1.5 g of crude drug per kilogram, p.o.), significantly reduced the immobility time in the forced swim test (FST) and tail suspension test (TST); moreover, the water extracts enhanced the 5-hydroxytryptophan (5-HTP)-induced head-twitch response and antagonized the action of reserpine in the mouse. We then explored the antidepressive mechanism of action of the ginsenoside Rb1 (Rb1) related to the brain-derived neurotrophic factor (BDNF) and its downstream proteins in mice exposed to chronic unpredictable mild stress (CUMS). Treatment with Rb1 (20 mg/kg, p.o.) for 21 days significantly attenuated the CUMS-induced decrease in the activities of BDNF, tropomyosin-related kinase B (TrkB), protein kinase B (AKT), extracellular regulatory protein kinase (ERK), and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the mouse hippocampal CA3 region and prefrontal cortex (PFC). Interestingly, treatment with the novel TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) did not alter the level of BDNF but significantly blocked the antidepressive effects of Rb1 on proteins downstream of BDNF in CUMS-treated mice. These results suggest that BDNF–TrkB–CREB signaling may be involved in the antidepressive mechanism of the action of Rb1.
Highlights
Depression is the leading cause of disability, with a prevalence greater than 20% in the global population (Lavanya et al, 2017)
We explored the mechanism of antidepressive action of the Rb1 via the brain-derived neurotrophic factor (BDNF)– tropomyosinrelated kinase B (TrkB)–CREB signaling pathway in the hippocampus and prefrontal cortex (PFC) of mice exposed to chronic unpredictable mild stress (CUMS)
Mouse Behavior in the open field test (OFT), TST, and forced swim test (FST) To assess the antidepressant-like effects of the different medicinal parts of ginseng, mice were pretreated with powders and extracts of the fibrous roots, main roots, or flower buds at the dose of 1.5 g of crude drug per kilogram
Summary
Depression is the leading cause of disability, with a prevalence greater than 20% in the global population (Lavanya et al, 2017). Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), play key roles in the pathogenesis of depression and serve many critical functions in neuronal maturation, synapse formation, and synaptic plasticity (Park and Poo, 2013). Deficiency of BDNF– TrkB–CREB function induces susceptibility to depression in rodents, while administration of BDNF–TrkB–CREB elicits antidepressant-like effects in animal models of depression (Hoshaw et al, 2005; Advani et al, 2009). These findings indicate that BDNF–TrkB–CREB signaling has potential as a therapeutic target in treating depression (Hashimoto et al, 2004; Hashimoto, 2010; Zhang et al, 2016)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
