Curcumin-primed exosomes mitigate endothelial cell dysfunction during hyperhomocysteinemia

Exosomes, the nano-units (<200 nm), released from diverse cell types in the extracellular body fluid, possess non-immunogenic property and ability to cross the blood-brain barrier (BBB). Since exosomes carry biological information from their cells of origin, we hypothesize that priming cells with potential therapeutic agents release improved cellular contents through exosomes. Curcumin possesses anti-oxidative and anti-inflammatory properties and provides a promising treatment for cerebral diseases and therefore, the aim of the study is to establish that mouse brain endothelial cells (MBECs) when primed with curcumin (7.5 μM), release an alleviated exosome population that can help recover the endothelial cell (EC) layer permeability.

Homocysteine is a well-known causative factor of BBB disruption; therefore, homocysteine-treated ECs were used as a model of BBB disruption and curcumin-primed exosomes were utilized to check their potential for mitigating EC disruption. MBECs were treated with curcumin and exosomes were isolated by using ultracentrifugation and immunoprecipitation. Expression levels of junction proteins were detected by Western blot and immunocytochemistry assays. Endothelial cell permeability was analyzed with Fluorescein isothiocyanate-Bovine serum albumin (FITC-BSA) leakage assay using transwell permeable supports.

Exosomes derived from curcumin-treated (primed) cells (CUR-EXO) alleviated oxidative stress, tight junctions (ZO-1, claudin-5, occludin), adherent junction (VE-cadherin) proteins and EC layer permeability induced during EC damage due to high homocysteine levels (hyperhomocysteinemia).

In conclusion, the study potentiates the use of CUR-EXO for cerebral diseases where drug delivery is still a challenge. The results also pave the way to novel translational therapies for cerebral diseases by maintaining and establishing therapeutic conservatories via primed exosomes.