Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating Nrf2

Sleep deprivation (SD) can induce cognitive and memory impairments. This impairment is in part due to oxidative stress damage in the hippocampus region of the brain. Corilagin (CL), a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica, shows strong antioxidant and neuroprotective effects. NF-E2-related factor (Nrf2)/heme oxygenase-1 (HO-1) and NADPH oxidase (NOX) are critical targets involved in cellular defense mechanisms against oxidative injury. Thus, we hypothesized that CL could be a preventive treatment for SD-induced memory impairments by inhibiting NOX2 and activating Nrf2. The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice. CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD (P < 0.05, p < 0.01) caused by SD. In hippocampal tissues, CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD (P < 0.05, P < 0.01). Meanwhile, in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL versus Glu-induced toxicity, while the effect of CL was enhanced in NOX2 siRNA-transfected neurons. Overall, these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2.