Novel application of brain-targeting polyphenol compounds in sleep deprivation-induced cognitive dysfunction

Wei Zhao, Jun Wang, Weina Bi, Mario Ferruzzi, Shrishailam Yemul, Daniel Freire, Paolo Mazzola, Lap Ho, Lauren Dubner, Giulio Maria Pasinetti

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Sleep deprivation produces deficits in hippocampal synaptic plasticity and hippocampal-dependent memory storage. Recent evidence suggests that sleep deprivation disrupts memory consolidation through multiple mechanisms, including the down-regulation of the cAMP-response element-binding protein (CREB) and of mammalian target of rapamycin (mTOR) signaling. In this study, we tested the effects of a Bioactive Dietary Polyphenol Preparation (BDPP), comprised of grape seed polyphenol extract, Concord grape juice, and resveratrol, on the attenuation of sleep deprivation-induced cognitive impairment. We found that BDPP significantly improves sleep deprivation-induced contextual memory deficits, possibly through the activation of CREB and mTOR signaling pathways. We also identified brain-available polyphenol metabolites from BDPP, among which quercetin-3-O-glucuronide activates CREB signaling and malvidin-3-O-glucoside activates mTOR signaling. In combination, quercetin and malvidin-glucoside significantly attenuated sleep deprivation-induced cognitive impairment in -a mouse model of acute sleep deprivation. Our data suggests the feasibility of using select brain-targeting polyphenol compounds derived from BDPP as potential therapeutic agents in promoting resilience against sleep deprivation-induced cognitive dysfunction.

Original languageEnglish
Pages (from-to)191-197
Number of pages7
JournalNeurochemistry International
StatePublished - 1 Oct 2015


  • Cognitive dysfunction
  • Memory consolidation
  • Polyphenols
  • Resilience
  • Sleep deprivation


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