Amyloid-β aggregation inhibitory and neuroprotective effects of xanthohumol and its derivatives for Alzheimer’s disease

Xueli Wang, See Lok Ho, Chung Yan Poon, Ting Yan, Hung Wing LI, Ricky M S WONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Background: Xanthohumol has been reported to have cytoprotection through activation of Nrf2−ARE signaling pathway and; it has capability of scavenging free radicals, suggesting its potential for the prevention of neurodegeneration. However, the bio-incompatibility and blood-brain barrier impermeability of xanthohumol hindered its in vivo efficacy potential for treating Alzheimer’s disease (AD). Objective: We designed and prepared a series of xanthohumol derivatives to enhance the desirable physical, biological and pharmacological properties in particular the blood-brain barrier permeability for intervention of AD. Methods: We designed and synthesized a novel series of 9 xanthohumol derivatives. Their inhibitory effect on amyloid-β (1-42), Aβ1-42, oligomerization and fibrillation as well as neuroprotection against amyloid-β induced toxicities, were explored. Results: Among the 9 xanthohumol derivatives, some of them exhibited a moderate to high inhibitory effect on Aβ1-42 oligomerization and fibrillation. They were biocompatible and neuroprotective to the SH-SY5Y cells by reducing the ROS generation and calcium uploading that were induced by the amyloid- β. Importantly, two of the derivatives were found to be blood-brain barrier permeable showing promising potential for AD treatment. Conclusion: Two derivatives have been identified to be biocompatible, non-toxic, neuroprotective against Aβ-induced toxicities and blood-brain barrier permeable highlighting their promising potential as AD drug candidates for future clinical use.

Original languageEnglish
Pages (from-to)836-842
Number of pages7
JournalCurrent Alzheimer Research
Volume16
Issue number9
DOIs
Publication statusPublished - 2019

Scopus Subject Areas

  • Neurology
  • Clinical Neurology

User-Defined Keywords

  • Amyloid aggregation inhibition
  • Blood-brain barrier permeable
  • Derivatives of xanthohumol
  • Neuroprotective

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