8-O-acetyl shanzhiside methylester protects against sleep deprivation-induced cognitive deficits and anxiety-like behaviors by regulating NLRP3 and Nrf2 pathways in mice.

Sleep deprivation (SD) is prevalent throughout the world, which has negative effects on cognitive abilities, and causing mood alterations. 8-O-acetyl shanzhiside methylester (8-OaS), a chief component in Lamiophlomis rotata (L. rotata) Kudo, possesses potent neuroprotective properties and analgesic effects. Here, we evaluated the alleviative effects of 8-OaS on memory impairment and anxiety in mice subjected to SD (for 72-h). Our results demonstrated that 8-OaS (0.2, 2, 20 mg/kg) administration dose-dependently ameliorated behavioral abnormalities in SD mice, accompanied with restored synaptic plasticity and reduced shrinkage and loss of hippocampal neurons. 8-OaS reduced the inflammatory response and oxidative stress injury in hippocampus caused by SD, which may be related to inhibition of NLRP3 inflammasome-mediated inflammatory process and activation of the Nrf2/HO-1 pathway. SD also led to increases in the expressions of TLR-4/MyD88, active NF-κB, pro-IL-1β, TNFα and MDA, as well as a decrease in the level of SOD in mice hippocampus, which were reversed by 8-OaS administration. Moreover, our molecular docking analyses showed that 8-OaS also has good affinity for NLRP3 and Nrf2 signaling pathways. These results suggested that 8-OaS could be used as a novel herbal medicine for the treatment of sleep loss and for use as a structural base for developing new drugs.