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ACS Chem Neurosci. 2019 Nov 20;10(11):4696-4703. doi: 10.1021/acschemneuro.9b00480. Epub 2019 Oct 21.

Inhibitory Effect of a Flavonoid Dihydromyricetin against Aβ40 Amyloidogenesis and Its Associated Cytotoxicity.

Jia L1,2,3,4, Zhao W3, Sang J3, Wang W3, Wei W3, Wang Y3, Zhao F3, Lu F1,2,3, Liu F1,2,3.

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Key Laboratory of Industrial Fermentation Microbiology , Ministry of Education , Tianjin 300457 , P. R. China.
Tianjin Key Laboratory of Industrial Microbiology , Tianjin 300457 , P. R. China.
College of Biotechnology , Tianjin University of Science and Technology , Tianjin 300457 , P. R. China.
College of Food Science and Engineering , Tianjin University of Science and Technology , Tianjin 300457 , P. R. China.


Misfolding and fibrillogenesis of amyloid-β protein (Aβ) play a key role in the onset and progression of Alzheimer's disease (AD). Screening for inhibitors against Aβ amyloidogenesis is helpful for rational designing and developing new anti-AD drugs and therapeutic strategies. Dihydromyricetin, a natural flavonoid extracted from a Chinese herb, Ampelopsis grossedentata, has been proven with antioxidative, anti-inflammatory, and neuroprotective effects against neurodegenerative disease. Herein, we found that dihydromyricetin could inhibit Aβ40 aggregation, impede the protofibril formation, disassemble preformed Aβ40 fibrils, and protect PC12 cells from the Aβ40-induced cytotoxicity using a series of biochemical and biophysical assays, including thioflavin T fluorescence, atomic force microscopy, and cell toxicity assays. Circular dichroism spectroscopy data proved that dihydromyricetin delayed the Aβ40 conformational conversion. In addition, the results of molecular dynamics simulations indicated that the interaction between dihydromyricetin and Aβ40 trimer is mainly nonpolar interactions. Key residues (i.e., V18, A21, and D23) of the Aβ40 interacting with dihydromyricetin were also identified. This study suggested that dihydromyricetin shows great potential to be developed as a novel Aβ40 inhibitor.


Alzheimer’s disease; Aβ40; Dihydromyricetin; fibrillogenesis; inhibitor; molecular dynamics simulations

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