Rb1, the Primary Active Ingredient in Panax ginseng C.A. Meyer, Exerts Antidepressant-Like Effects via the BDNF–Trkb–CREB Pathway

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.

Ginsenoside Rb1 induces a pro-neurogenic microglial phenotype via PPARγ activation in male mice exposed to chronic mild stress

“…A subset of stressed animals was pretreated with PPARγ inhibitor GW9662 (1 mg/kg/day in 1% DMSO, i.p., 28 d; Med Chem Express, Monmouth Junction, NJ, USA), then treated 1 h later with GRb1 (control mice were administrated with 1% DMSO solution in 0.9% saline). The doses of GRb1 and IMI were chosen based on previous studies [ 30 , 31 ]. After intragastric administration for 0.5 h, 1 h, 2 h, 3 h, 12 h, 24 h, and 48 h, the concentration of GRb1 in hippocampus tissues was detected by LC-MS/MS technique.…”

Morinda officinalis oligosaccharides ameliorate depressive‐like behaviors in poststroke rats through upregulating GLUT3 to improve synaptic activity

“…The TST was carried out according to the conventional method described by previous research 27 Briefly, rats were suspended 50 cm above the floor with their tail attached to a rope for 6 minutes. The immobility and climbing time were identified as previously described.…”

“…Before the other behavioral tests, the OFT was performed according to the procedure reported in a previous study 27 to exclude the interference of motor abnormalities. Rats were individually placed in a corner of a square wooden box (100 cm × 100 cm × 50 cm) for 5 minutes.…”

α-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3/ROS Mediated NLRP3 Inflammasome Deactivation

“…Depression is a psychiatric disorder which affects more than one-fifth of the global population ( Wang et al, 2019 ). It causes considerable burden on individuals and society with its high morbidity, recurrence, and mortality ( Feng et al, 2019 ).…”