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The sleeplessness was introduced to all rats except control. Before and after administration with vehicle or pearl powder, cognition was evaluated by Morris water maze (MWM). The protein expression in hippocampus among all groups was examined using iTRAQ\u2010based global proteomic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Morris water maze tests revealed improvements of insomnia\u2010induced cognitive deficit in both PP\u2010 and ES\u2010treated rats, as compared to SD rats. However, proteomic analysis indicates that the pharmacological impact on gene expression of these two medicines is quite different: pearl is more capable of correcting aberrant gene expression caused by SD than estazolam. Therefore, pearl is more suitable for treatment of insomnia. These data, together with protein\u2010protein interaction analysis, indicate that several pathways, affected by sleep deprivation, may be rescued by pearl powder: retrograde endocannabinoid signalling pathway, and the protein interaction or network enrich in oxidative phosphorylation Parkinson's disease and Huntington disease, etc<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Sleep deprivation can mimic cognition decline caused by insomnia with altered protein expression in the hippocampus; such behavioural and pathological changes can be significantly ameliorated by pearl powder.<\/jats:p>\n                  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