Hopeahainol A attenuates memory deficits by targeting β‐amyloid in APP / PS 1 transgenic mice

• Published in: Aging cell 2013-02, Vol.12 (1), p.85-92
• Main Authors: Zhu, Xiaolei, Ye, Lan, Ge, Huiming, Chen, Ling, Jiang, Nan, Qian, Lai, Li, Lingling, Liu, Rong, Ji, Shen, Zhang, Su, Jin, Jiali, Guan, Dening, Fang, Wei, Tan, Renxiang, Xu, Yun
• Format: Article
• Language: English
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12022

Increasing evidence demonstrates that amyloid beta ( A β) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of A lzheimer's disease ( AD ). Identification of the molecules targeting A β is thus of particular significance in the treatment of AD . Hopeahainol A ( H op A ), a polyphenol with a novel skeleton obtained from H opea hainanensis , is potentially acetylcholinesterase‐inhibitory and anti‐oxidative in H 2 O 2 ‐treated PC 12 cells. In this study, we reported that H op A might bind to A β 1–42 directly and inhibit the A β 1–42 aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that H op A decreased the interaction between A β 1–42 and A β‐binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro . In addition, H op A was able to rescue the long‐term potentiation induction by protecting synaptic function and attenuate memory deficits in APP / PS 1 mice. Our data suggest that H op A might be a promising drug for therapeutic intervention in AD .