Formononetin attenuates Aβ25-35-induced adhesion molecules in HBMECs via Nrf2 activation.

Abstract

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.

• Authors: Mingyue Fan, Zhe Li, Ming Hu, Haifeng Zhao, Tianjun Wang, Yanqiu Jia, Rui Yang, Shuo Wang, Jiaxi Song, Yang Liu, Wei Jin
• Journal: Brain research bulletin (Brain Res Bull) Vol. 183 Pg. 162-171 (06 01 2022) ISSN: 1873-2747 [Electronic] United States
• PMID: 35304289 (Publication Type: Journal Article)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Amyloid beta-Peptides
• Cell Adhesion Molecules
• Isoflavones
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Peptide Fragments
• formononetin

Topics

• Amyloid beta-Peptides (metabolism)
• Brain (metabolism)
• Cell Adhesion Molecules (metabolism)
• Endothelial Cells (metabolism)
• Humans
• Isoflavones (pharmacology)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Neuroprotective Agents (pharmacology)
• Peptide Fragments (metabolism)