Protopanaxadiol-type ginsenosides ameliorate PTSD-like memory impairment and neuroinflammation in rats via suppression of TLR4/NF-κB signaling

Post-traumatic stress disorder (PTSD) is a serious psychiatric condition that develops after exposure to intense or traumatic stress. Ginsenosides, the primary bioactive compounds of ginseng, have been reported to enhance cognitive performance. Protopanaxadiol (PD) and protopanaxatriol (PT) are two major classes of triterpenoid saponins. In the present study, a PTSD-like rat model was established using the single prolonged stress (SPS) paradigm, and the effects of PD and PT on memory dysfunction were evaluated. After SPS exposure, male rats received daily intraperitoneal administration of PD (10 or 20 mg/kg) or PT (10 and 20 mg/kg) for 14 days. PD treatment significantly improved both spatial and cognitive memory compared with PT treatment. PD also suppressed the elevation of pro-inflammatory cytokines in the prefrontal cortex and hippocampus, and mitigated the reduction in brain-derived neurotrophic factor mRNA expression in the hippocampus. In addition, PD attenuated the upregulation of Toll-like receptor 4 (TLR4) and nuclear factor (NF)-κB protein expression in the hippocampus. By contrast, PT treatment did not produce meaningful changes in memory performance or inflammatory markers. These findings suggest that the beneficial effects of PD are associated with anti-inflammatory activity that may involve modulation of the TLR4/NF-κB signaling pathway.