Emodin inhibits aggregation of amyloid-β peptide 1-42 and improves cognitive deficits in Alzheimer's disease transgenic mice

J Neurochem. 2021 Jun;157(6):1992-2007. doi: 10.1111/jnc.15156. Epub 2020 Oct 12.


Aggregation of amyloid-β peptide 1-42 (Aβ42) initiates the onset of Alzheimer's disease (AD), and all the drugs designed to attenuate AD have failed in clinical trials. Emodin reduces levels of β-amyloid, tau aggregation, oxidative stress, and inflammatory response, demonstrating AD therapeutic potential, whereas its effect on the accumulation of the amyloid-β protein is not well understood. In this work, we investigated emodin activity on Aβ aggregation using a range of biochemical, biophysical, and cell-based approaches. We provide evidence to suggest that emodin blocks Aβ42 fibrillogenesis and Aβ-induced cytotoxicity, displaying a greater effect than that of curcumin. Through adopting three short peptides (Aβ1-16, Aβ17-33, and Aβ28-42), it was proven that emodin interacts with the Leu17-Gly33 sequence. Furthermore, our findings indicated that Val18 and Phe19 in Aβ42 are the target residues with which emodin interacts according amino acid mutation experiments. When fed to 8-month-old B6C3-Tg mice for 2 months, high-dose emodin ameliorates cognitive impairment by 60%-70%. Pathological results revealed that levels of Aβ deposition in the brains of AD mice treated with a high dose of emodin decreased by 50%-70%. Therefore, our study indicates that emodin may represent a promising drug for AD treatment.

Keywords: Alzheimer's disease; Aβ42 aggregation; cognitive decline; emodin; senile plaque.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism
  • Emodin / pharmacology
  • Emodin / therapeutic use*
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / toxicity*
  • Protein Aggregates / drug effects*
  • Protein Aggregates / physiology
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use


  • Amyloid beta-Peptides
  • Peptide Fragments
  • Protein Aggregates
  • Protein Kinase Inhibitors
  • amyloid beta-protein (1-42)
  • Emodin