LAUSR

Tenuifolin (TEN), a natural neuroprotective compound obtained from the Polygala tenuifolia Willd plant, has improved cognitive symptoms. However, the impact of TEN on memory impairments caused by sleep deprivation (SD) is unclear. Accordingly, the objective of this study was to investigate the mechanisms behind the preventative benefits of TEN on cognitive impairment caused by SD. TEN (10 and 20 mg/kg) and Huperzine A (0.1 mg/kg) were given to mice through oral gavage for 28 days during the SD process. The results indicate that TEN administrations improve short‐ and long‐term memory impairments caused by SD in the Y‐maze, object identification, and step‐through tests. Moreover, TEN stimulated the generation of anti‐inflammatory cytokines (interleukin‐10), lowered the production of pro‐inflammatory cytokines (interleukin‐1β, interleukin‐6, and interleukin‐18), and activated microglia, improving antioxidant status in the hippocampus. TEN treatments significantly boosted the expression of nuclear factor erythroid 2‐related factor 2 and heme oxygenase‐1 while considerably decreasing the expression of NOD‐like receptor thermal protein domain associated protein 3 and caspase‐1 p20. Additionally, TEN restored the downregulation of the brain‐derived neurotrophic factor signaling cascade and the impaired hippocampal neurogenesis induced by SD. When considered collectively, our data suggest that TEN is a potentially effective neuroprotective agent for cognition dysfunction.