Bound polyphenols from seabuckthorn pomace alleviate sleep deprivation-induced cognitive impairment via gut microbiota-driven homovanillic acid-mediated neuroprotection.

Polyphenols exhibit potential neuroprotective activity. Seabuckthorn pomace bound polyphenols (SBP), as key bioactives from seabuckthorn, mainly contain ellagic acid, kaempferol, rutin, salvianolic acid A, and isorhamnetin. Chronic sleep deprivation (SD) leads gut microbiota dysbiosis and systemic inflammation, impairs neuronal and synaptic structural integrity, induces cognitive dysfunction, and increases the risk of neurodegenerative diseases. However, the ameliorative effects and underlying molecular mechanisms of SBP against SD-induced cognitive impairment remain unclear. The study investigated the improving effects and underlying mechanisms of dietary SBP supplementation on cognitive injury induced by chronic SD in mice. Behavioral results showed that 45 mg·kg-1·d-1 SBP significantly alleviated cognitive dysfunction in SD mice. Meanwhile, SBP ameliorated intestinal inflammation, gut microbial imbalance and tyrosine metabolism disorder, and markedly enriched beneficial bacteria including Bifidobacterium, Lactobacillus and Ligilactobacillus, with increased homovanillic acid (HVA) levels in feces, serum and brain. Furthermore, SBP attenuated SD-induced neuronal and synaptic damage and upregulated synaptic proteins SYN1 and PSD-95, which was associated with HVA-mediated inhibition of LC3/P62 autophagy pathway and activation of BDNF/TrKB pathway. Overall, SBP improves SD-induced synaptic damage and cognitive impairment via the gut microbiota-HVA-brain axis. These results position SBP can be used as a functional active factor in food development with memory-improving potential.