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.
Keywords: (24R)-pseudo-ginsenoside HQ; (24S)-pseudo-ginsenoside HQ; LPS-induced depression; ginsenoside Rh2.