Peptide WCPFSRSF alleviates sleep deprivation-induced memory impairment by inhibiting neuroinflammation and modulating IL-6/JAK/STAT signaling pathway

Our previous study revealed that Trp-Cys-Pro-Phe-Ser-Arg-Ser-Phe (WCPFSRSF) exerted memory-improving ability in sleep-deprived mice; however, the underlying regulatory network was still unclear. The purpose of this study was to evaluate the effects of WCPFSRSF in sleep-deprived mice and to clarify the main regulatory networks. Our results showed that WCPFSRSF ameliorated the abnormal morphology of neurons and loss of neurons in hippocampus of sleep-deprived mice. Furthermore, WCPFSRSF inhibited oxidative stress via enhancing the activities of antioxidant enzymes, reducing MDA levels and activating the Nrf2 pathway. Transcriptome analysis showed that WCPFSRSF mainly regulated inflammation-related pathways, such as IL-17, TNF and JAK/STAT pathways. Further analysis showed that WCPFSRSF reduced the release of pro-inflammatory cytokines and the expression of microglia marker Iba-1 and astrocyte marker GFAP, thereby inhibiting neuroinflammation. Western Blotting analysis showed that WCPFSRSF regulated the IL-6/JAK/STAT pathway. In addition, WCPFSRSF and its in silico gastrointestinal digested fragments WCP and FSR were potential JAK2/STAT3 inhibitors. WCPFSRSF and WCP could reduce the NO levels in LPS-treated BV-2 cells. Collectively, our results indicated that WCPFSRSF improved memory impairment induced by sleep deprivation through inhibiting glial cell activation and neuroinflammation.

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