Hemerocallis Citrina Baroni Ameliorates Chronic Sleep Deprivation-Induced Cognitive Deficits and Depressive-Like Behaviours in Mice

Sleep deprivation (SD) is common during spaceflight. SD is known to cause cognitive deficits and depression, requiring treatment and prevention. Hemerocallis citrina Baroni (Liliaceae) is a perennial herb with antidepressant, antioxidant, antitumor, anti-inflammatory, and neuroprotective effects.The aim of our study was to investigate the effects of H. citrina extract (HCE) on SD-induced cognitive decline and depression-like behavior and possible neuroinflammation-related mechanisms. HCE (2 g/kg/day, i.g.) or vortioxetine (10 mg/kg/day, i.g.) were given to mice by oral gavage for a total of 28 days during the SD process. HCE treatment was found to ameliorate SD-induced impairment of short- and long-term spatial and nonspatial memory, measured using Y-maze, object recognition, and Morris water maze tests, as well as mitigating SD-induced depression-like behaviors, measured by tail suspension and forced swimming tests. HCE also reduced the levels of inflammatory cytokines (IL-1β, IL-18, and IL-6) in the serum and hippocampus. Furthermore, HCE suppressed SD-induced microglial activation in the prefrontal cortex (PFC) and the CA1 and dentate gyrus (DG) regions of the hippocampus. HCE also inhibited the expression of phosphorylated NF-κB and activation of the NLRP3 inflammasome. In summary, our findings indicated that HCE attenuated SD-induced cognitive impairment and depression-like behavior and that this effect may be mediated by the inhibition of inflammatory progression and microglial activation in the hippocampus, as well as the down-regulation of NF-κB and NLRP3 signaling. The findings of these studies showingTthese results indicate that HCE exerts neuroprotective effects and are consistent with the findings of previous studies, suggesting that HCE is beneficial for the prevention and treatment of cognitive decline and depression in SD.