Ginsenoside Rg1 Improves PTSD‐Like Sleep Disturbances in Male Mice: Involvement of NLRP3‐Related Inflammatory and Apoptotic Pathways

Sleep disturbances (SD) are not merely symptoms of posttraumatic stress disorder (PTSD), but also amplify and perpetuate all other PTSD phenotypes. Ginsenoside Rg1 is extensively applied in managing neuropsychiatric diseases. Nevertheless, its impact on PTSD-like SD and mechanisms remain largely unknown. In this study, the PTSD model in mice was produced using single-prolonged stress (SPS) and the improvement effect of ginsenoside Rg1 on PTSD-like behavior in mice, especially the sleep-wake phase was detected. The potential targets and signaling pathways of ginsenoside Rg1 as an intervention for treatment of PTSD with sleep disturbances (PTSD-SD) were predicted using bioinformatics analysis. Thereafter, in vivo experiments were further used to verify the results. Our data showed that 14 days after SPS, the sleep architecture of mice was significantly disturbed, while ginsenoside Rg1 could treat PTSD-like SD in SPS mice. The results of bioinformatics analysis suggested that NLRP-related pathways and apoptosis may be the key factors for ginsenoside Rg1 to treat PTSD-like sleep disturbances. Meanwhile, animal experiments also showed that the NLRP3 inflammasome, oxidative stress and apoptosis-related markers were abnormally expressed in the hippocampus of SPS mice, but the administration of ginsenoside Rg1 could counteract the dysregulated expression of the above proteins in SPS mice. Finally, the results of docking revealed that ginsenoside Rg1 had favorable binding affinity with verified targets including NF-κB, NLRP3, ASC, GFAP, HO-1, and cleaved caspase-3. Collectively, ginsenoside Rg1 is effective to prevent PTSD-like SD, likely by regulating systemic comprehensive responses.