Objectives: Anthocyanin-rich diet can preserve cognitive decline and prevent or delay the development of neurogenerative disorders. It has been shown that an increase in blood-brain barrier permeability, regulated by brain endothelial cells, is the key factor in the development of this disorder. However, the molecular mechanisms underlying these health properties are still largely unknown. The aim of this study was to identify the capacity of anthocyanins to prevent an inflammatory-induced increase in endothelial cell permeability and decipher the in-depth underlying molecular mechanism of action using a multi-genomic approach.
Methods: Human brain microvascular endothelial cells were exposed to phase two metabolites and gut microbiome-derived metabolites prior to induction of inflammatory stress using TNF alpha. The adhesion of immune cells to HBMEC and their permeability to immune cells were assessed in vitro. Total RNA was extracted and global genomic analyzed using genomic microarrays followed by in-depth bioinformatic analysis.
Results: We observed that anthocyanin metabolites can diminish inflammatory-induced adhesion of monocytes to endothelial cells and diminish cell permeability to immune cells. These effects were associated with the capacity of metabolites to modulate the global expression of protein-coding genes but also non-coding genes, including miRNAs, lncRNAs and snoRNAs. Bioinformatic analysis showed that these genes and target genes of non-coding RNAs are involved in the regulation of cell-cell interactions, cytoskeleton organization, focal adhesion, and chemotaxis. In-silico docking analysis showed that these metabolites can interact with transcription factors and cell signaling proteins. Global genomic profile was observed to be inversely correlated with genomic modification in patients with no regenerative disorders.
Conclusions: In conclusion, anthocyanin metabolites can prevent inflammatory-induced blood-brain barrier permeability by maintaining endothelial cell functions through multi-genomic mode action, presenting relevant cellular and molecular mechanisms underlying their neurocognitive protective properties.
