Combined metabolomics and network pharmacology explore the protective mechanism of bornyl acetate against cognitive impairment in chronic sleep-deprived mice

Abstract Chronic sleep deprivation (CSD) is currently a serious global public health concern, and CSD induces numerous diseases, including cognitive impairment. Bornyl acetate (BA) possesses a brilliant anti-inflammatory activity and plays a favorable role in neuroinflammation. The purpose of this research was to explore the efficacy and the underlying mechanism of BA in cognitive dysfunction caused by CSD. The CSD mouse model was established using a modified multiplatform method. Experimental techniques such as Morris water maze test, tissue staining, western blot, enzyme-linked immunosorbent assay, metabolomics and network pharmacology were used for the study. The results showed that CSD induced hippocampal neuronal damage and neuroinflammation, leading to impaired learning and memory functions in mice. BA intervention reversed these damages, inhibited neuroinflammation, and improved learning and memory functions in mice, which may be related to the inhibition of TLR4/NF-κB signaling pathway. Metabolomics analysis showed that 29 metabolites underwent significant changes after BA intervention, involving arachidonic acid metabolism, glycerophospholipid metabolism, tyrosine metabolism, and glyceride metabolism. Further analyses combined metabolomics and network pharmacology, and 10 core targets on BA modulation of CSD-induced cognitive dysfunction were identified. KEGG enrichment analysis suggested that PPAR signaling pathway, Th17 cell differentiation, Non-alcoholic fatty liver disease, Lipid and atherosclerosis, Adipocytokine signaling pathway and Efferocytosis signaling pathway may be important mechanisms by which BA ameliorates CSD-induced cognitive dysfunction. Our study identifies multiple candidate targets and signaling pathways associated with BA against CSD-triggered cognitive dysfunction, which may provide theoretical references for subsequent research on BA and related exploratory strategies.