Study on Antidepressant Activity of Pseudo-Ginsenoside HQ on Depression-Like Behavior in Mice.

Suppressive effects of ginsenoside Rh₂ (Rh₂), (24)-pseudo-ginsenoside HQ (-PHQ), and (24)-pseudo-ginsenoside HQ (-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, -PHQ, and -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, -PHQ and -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 -PHQ was found related to the dopaminergic (DA), γ-aminobutyric acid (GABA)ergic, and noradrenaline systems, while the antidepressive effect of -PHQ was involved in the DA and GABAergic systems. Taken together, these results suggested that Rh₂, -PHQ, and -PHQ produced significant antidepressant-like effects, which may be related to the BDNF/TrkB and Sirt1/NF-κB signaling pathways.