Ginseng Total Saponins Reverse Corticosterone-Induced Changes in Depression-Like Behavior and Hippocampal Plasticity-Related Proteins by Interfering with GSK-3β-CREB Signaling Pathway
This study aimed to explore the antidepressant mechanisms of ginseng total saponins (GTS) in the corticosterone-induced mouse depression model. In Experiment 1, GTS (50, 25, and 12.5？mg？kg？1？d？1, intragastrically) were given for 3 weeks. In Experiment 2, the same doses of GTS were administrated after each corticosterone (20？mg？kg？1？d？1, subcutaneously) injection for 22 days. In both experiments, mice underwent a forced swimming test and a tail suspension test on day 20 and day 21, respectively, and were sacrificed on day 22. Results of Experiment 1 revealed that GTS (50 and 25？mg？kg？1？d？1) exhibited antidepressant activity and not statistically altered hippocampal protein levels of brain-derived neurotrophic factor (BDNF) and neurofilament light chain (NF-L). Results of Experiment 2 showed that GTS (50 and 25？mg？kg？1？d？1) ameliorated depression-like behavior without normalizing hypercortisolism. The GTS treatments reversed the corticosterone-induced changes in mRNA levels of BDNF and NF-L, and protein levels of BDNF NF-L, phosphor-cAMP response element-binding protein (Ser133), and phosphor-glycogen synthase kinase-3β (Ser9) in the hippocampus. These findings imply that the effect of GTS on corticosterone-induced depression-like behavior may be mediated partly through interfering with hippocampal GSK-3β-CREB signaling pathway and reversing decrease of some plasticity-related proteins. 1. Introduction Ginseng, the root of Panax ginseng C. A. Meyer (Araliaceae), is one of the most famous and valuable forms of traditional herbal medicine that has been widely applied for thousands of years. The early Chinese used ginseng as a general tonic and adaptogen to help the body to resist the adverse influence of a wide range of physical, chemical, and biological factors and to restore homeostasis [1]. Ginseng total saponins (GTS) are considered the principal bioactive ingredients behind claims of ginseng efficacy [2]. Recently, ginseng and ginsenosides have been shown to have several beneficial functions in the brain, including antidepressant or antistress effects. Our previous studies have shown that the water-based extract of ginseng exhibited protection against the hypercortisolism-induced impairment of hippocampal neurons without reversing the increased plasma corticosterone level [3, 4]. Some researchers reported that acute ginsenoside Rg1 treatment had antidepressant activity, as shown in a forced swimming test (FST) and a tail suspension test (TST) [5]. The antidepressant effects of ginsenosides administrated subacutely to normal mice or chronically to the
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