Ophiopogon polysaccharide can improve memory impairment induced by sleep deprivation in aged rats by regulating gut microbiota and inhibiting TLR4/NF-κB pathway in hippocampus

Abstract

Background: Sleep deprivation (SD) is highly prevalent among the elderly population and accelerates cognitive decline through mechanisms such as neuroinflammation and disruption of the gut-brain axis. This study aims to investigate whether Ophiopogon polysaccharides (OPS) can improve memory impairment induced by SD in aged rats by modulating the gut microbiota and inhibiting the TLR4/NF-κB pathway in the hippocampus. A modified multi-platform method was employed to administer treatment to 20-month-old male Sprague-Dawley rats following seven days of sleep deprivation. The Morris water maze test, HE staining, ELISA, 16S rRNA sequencing, and Western blotting were conducted for histological and molecular biological analyses.The anti-inflammatory and neuroprotective effects of OPS were further validated in LPS-stimulated BV2 microglial cells and a BV2-HT22 co-culture system. The results demonstrated that OPS significantly ameliorated spatial memory deficits in sleep-deprived rats, alleviated hippocampal neuronal damage, reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6), and restored the balance of neurotransmitters (DA, 5-HT). 16S rRNA sequencing revealed that OPS modulated the gut microbiota structure, increased the abundance of potential probiotic taxa such as norank_f__Muribaculaceae and Faecalibacterium, and decreased the abundance of potential pro-inflammatory genera such as Oscillibacter and Romboutsia. Western blot analysis indicated that OPS inhibited the activation of the TLR4/NF-κB signaling pathway in the hippocampus. In vitro experiments confirmed that OPS could inhibit the LPS-induced inflammatory response in BV2 microglial cells and reduce microglia-mediated neuronal apoptosis in HT22 cells. These findings suggest that OPS may serve as a promising therapeutic agent for mitigating cognitive impairment caused by sleep deprivation, exerting its effects through multi-target mechanisms, including modulation of gut microbiota and suppression of hippocampal TLR4/NF-κB-mediated neuroinflammatory pathways.