(P29-019-24) Curcumin Exert Multigenomic Modification in Brain Microvascular Endothelial Cells in Mice on a High Glycemic Diet

Objectives: Studies have shown that curcumin possesses anti-inflammatory properties and can prevent endothelial cell dysfunction, diminishing the development of atherosclerosis. Brain endothelial cells play an important role in regulating blood-brain barrier (BBB) permeability, dysfunction of which has been identified as a key risk factor in the development of cognitive disorders and neurodegenerative diseases. However, the molecular mechanism of curcumin in brain endothelial cells is little explored.

Methods: This study aimed to decipher in-depth mechanisms of action of curcumin in hippocampal brain microvessels  of mice on a high glycemic diet (HGD). Wild-type male mice were fed a low glycemic diet (LGD, 12% sucrose/weight) or an HGD (34% sucrose/weight) with/without curcumin (0.02% in diet) for 12 weeks. Brain hippocampal microvascular cells were isolated using laser capture microdissection, total RNA was extracted, and global gene expression was assessed by microarray.

Results: We observed that global hippocampal microvascular gene expression was significantly modulated by curcumin, and that it partly corrected changes in gene expression induced by high glycemic stress. Curcumin affected the expression of not only protein-coding genes but also non-coding genes, such as miRNAs, lncRNAs, and snoRNAs. Bioinformatic analyses showed that genes which expression has been modulated by curcumin and target genes of non-coding RNAs are implicated in the regulation of cell cytoskeleton, cell-cell interaction, anti-inflammatory response, or cell signaling, all of which regulate endothelial cell permeability. In-silico 3D docking showed potential interaction between curcumin metabolites and potential transcription factors.

Conclusions: Taken together, these results revealed novel and in-depth mechanisms of action of curcumin in brain endothelial cells, associated with decreased endothelial permeability and therefore BBB permeability.

Funding Sources: N/A