Neuroprotective effect of formononetin in ameliorating learning and memory impairment in mouse model of Alzheimer's disease

• Published in: Bioscience, biotechnology, and biochemistry biotechnology, and biochemistry, 2018-01, Vol.82 (1), p.57-64
• Main Authors: Fei, Hong-Xin, Zhang, Ying-Bo, Liu, Ting, Zhang, Xiao-Jie, Wu, Shu-Liang
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer's disease; amyloid beta peptide; Animals; Drug Delivery Systems; Formononetin; Humans; Isoflavones - therapeutic use; low-density lipoprotein-associated protein 1; Mice; Neuroprotective Agents - therapeutic use; receptor for advanced glycation end products; Receptor for Advanced Glycation End Products - drug effects; Receptors, LDL - drug effects; Tumor Suppressor Proteins - drug effects
• ISSN: 0916-8451; 1347-6947
• DOI: 10.1080/09168451.2017.1399788

Alzheimer's disease (AD) is the most common cause of dementia among elderly population. Deranged β-amyloid (Aβ) trafficking across the blood-brain barrier is known to be a critical element in the pathogenesis of AD. In the vascular endothelial cells of hippocampus, Aβ transport is mainly mediated by low-density lipoprotein-associated protein 1 (LRP1) and the receptor for advanced glycation end (RAGE) products; therefore, LRP1 and RAGE endothelial cells are potential therapeutic targets for AD. In this study, we explored the effects of Formononetin (FMN) on learning and memory improvement in APP/PS1 mice and the related mechanisms. We found that FMN significantly improved learning and memory ability by suppressing Aβ production from APP processing, RAGE-dependent inflammatory signaling and promoted LRP1-dependent cerebral Aβ clearance pathway. Moreover, FMN treatment alleviated ultrastructural changes in hippocampal vascular endothelial cells. In conclusion, we believe that FMN may be an efficacious and promising treatment for AD. Formononetin ameliorates learning and memory impairment in mouse model of Alzheimer's disease via suppressing inflammatory signaling and promoted Aβ clearance.