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

Lichun Wang, Sitong Liu, Jiaqi Xu, Nobumoto Watanabe, Kevin H. Mayo, Jiang Li, Xiaomeng Li

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1992-2007
Number of pages16
JournalJournal of Neurochemistry
Volume157
Issue number6
Early online dateAug 16 2020
DOIs
StatePublished - Jun 2021

Bibliographical note

Funding Information:
This study was supported by the Ministry of Science and Technology (2016YFE0128500), Jilin Provincial Science & Technology Department (20180414057GH, 20170204009YY), Changchun Science & Technology Department (17YJ006, 17YJ001), Jilin Province Development and Reform Commission (2016C047‐3, 2016C048‐3), University S & T Innovation Platform of Jilin Province for Economic Fungi (#2014B‐1), the National Natural Science Foundation of China (No. 31870758, 30871301), and the Program for Introducing Talents to Universities (No. B07017).

Publisher Copyright:
© 2020 International Society for Neurochemistry.

Keywords

  • Alzheimer's disease
  • Aβ42 aggregation
  • cognitive decline
  • emodin
  • senile plaque
  • Emodin/pharmacology
  • Male
  • Mice, Transgenic
  • Animals
  • Peptide Fragments/antagonists & inhibitors
  • Cognitive Dysfunction/drug therapy
  • Alzheimer Disease/drug therapy
  • Female
  • Mice
  • Protein Kinase Inhibitors/pharmacology
  • Protein Aggregates/drug effects
  • Amyloid beta-Peptides/antagonists & inhibitors

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Journal Article

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