Abstract
Suppressive effects of ginsenoside Rh2 (Rh2), (24R)-pseudo-ginsenoside HQ (R-PHQ), and (24S)-pseudo-ginsenoside HQ (S-PHQ) against lipopolysaccharide (LPS)-induced depression-like behavior were evaluated using the forced swimming test (FST) and tail suspension test (TST) in mice. Pretreatment with Rh2, R-PHQ, and S-PHQ significantly decreased immobility time in FST and TST with clear dose-dependence, and significantly downregulated levels of serum tumor necrosis factor-α and interleukin-6, and upregulated superoxide dismutase activity in the hippocampus of LPS-challenged mice. Furthermore, R-PHQ and S-PHQ significantly increased the expression of the brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), sirtuin type 1 (Sirt1), and nuclear-related factor 2, and inhibited the phosphorylation of inhibitor of κB-α and nuclear factor-κB (NF-κB) in the hippocampus of LPS-challenged mice. Additionally, the antidepressant-like effect of R-PHQ was found related to the dopaminergic (DA), γ-aminobutyric acid (GABA)ergic, and noradrenaline systems, while the antidepressive effect of S-PHQ was involved in the DA and GABAergic systems. Taken together, these results suggested that Rh2, R-PHQ, and S-PHQ produced significant antidepressant-like effects, which may be related to the BDNF/TrkB and Sirt1/NF-κB signaling pathways.
Highlights
Major depressive disorder (MDD) is a common psychiatric disorder, which is widely distributed in the population [1,2]
The results showed that LPS exposure, or drug administration of fluoxetine (FLU), Rh2, (24R)-pseudo-ginsenoside HQ (R-PHQ), or
We firstly reported the antidepressive effects of Rh2, R-PHQ, and -pseudo-ginsenoside HQ (S-PHQ) using
Summary
Major depressive disorder (MDD) is a common psychiatric disorder, which is widely distributed in the population [1,2]. LPS can activate mitogen-activated protein kinases (MAPK) in cells, or nuclear factor signal transduction pathways and corresponding transcription factors This provided reason to regulate inflammatory mediators via the expression of IL-1, TNF-α, and so on, further releasing nitric oxide, tumor necrosis factor, interleukin, free radicals, and a large number of toxic cytokines, resulting in the body suffering oxidative stress and inflammation reactions [7,8]. These cytokines could further result in oxidative stress, characterized by suppressed superoxide dismutase (SOD) activity and elevated malondialdehyde level in the hippocampus, which are considered as the mechanisms of LPS-induced depression [9]
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