The aim of this study was to investigate the effect of asperosaponin VI (ASA VI) on cognitive function in sleep-deprived mice and the related mechanisms.C57BL/6J mice were subjected to sleep deprivation by multi-platform water environment method,during which the mice were intraperitoneally injected with ASA VI.New object recognition test and Morris water maze test were used to evaluate the cognitive function of mice.The changes in the inflammatory levels,neurogenesis and signaling pathways in hippocampus were detected by q-PCR,immunohistochemistry and Western blotting.The results showed that compared with the control group,microglia in the hippocampus of the sleep-deprived mice were activated,the expression level of inflammatory cytokines was significantly increased (P < 0.05),the number of newborn neurons was significantly decreased (P < 0.05),and the cognitive function was decreased.The ASA VI intervention group significantly improved the cognitive ability of sleep-deprived mice,inhibited the expressions of pro-inflammatory cytokines IL-1β,TNF-α and IL-6 in hippocampus (P < 0.05),and significantly increased the expression levels of anti-inflammatory cytokines IL-4 and IL-10 and neurotrophic factor BDNF (P < 0.05).At the same time,the protein expression levels of p-PI3K,PI3K and Akt,as well as the number of new neurons in hippocampus were increased by the intervention of ASA VI (P < 0.05).Treatment with PI3K/Akt inhibitor LY294002 significantly reduced the intervention effect of ASA VI on sleep-deprived mice.These results suggested that ASA VI could improve the learning and memory of sleep-deprived mice,and its mechanism was related to the activation of PI3K/Akt signaling pathway.ASA VI has potential development prospects as an anti-inflammatory and neuroprotective drug.