Brain vascular
inflammation plays a crucial role in the pathogenesis of
Alzheimer's disease (AD). As a central pathogenic factor in AD, the extracellular buildup of
amyloid-β (Aβ) induces brain microvascular endothelial cells activation, impairs endothelial structure and function.
Formononetin (
FMN) has been reported to protect against
Alzheimer's disease (AD) and attenuates vascular
inflammation in
atherosclerosis. However, its involvement in regulating vascular
inflammation of AD has not been investigated. In the study, we found that
FMN significantly attenuates Aβ25-35-induced expression of adhesion molecules, including intracellular adhesion molecule-1 (ICAM-1) and
vascular cell adhesion molecule-1 (VCAM-1) in the human brain microvascular endothelial cells (HBMECs), suggesting that
FMN inhibits Aβ25-35-induced brain endothelial cells inflammatory response. Moreover, we observed that
FMN attenuates Aβ25-35-induced translocation of NFκB (p65) into the nucleus of HBMECs, and found that
FMN treatment induces Nrf2 expression and attenuates Nrf2-Keap1 association in a dose-dependent manner in HBMECs. Furthermore, we demonstrated that Nrf2 silencing significantly attenuates
FMN-reduced NFκB (p65) activation and nuclear translocation. Lastly, our results showed that
FMN treatment attenuates Aβ25-35-induced adhesion of THP-1 cell to endothelial cell monolayer. Collectively, these findings suggest that
FMN attenuates Aβ25-35-induced activation in human brain microvascular endothelial cells, which at least in part was mediated through Nrf2 pathways.