Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer's Diseases.
Alzheimer Disease
/ drug therapy
Amyloid beta-Peptides
/ metabolism
Animals
Blood-Brain Barrier
/ drug effects
Calcium
/ metabolism
Capillary Permeability
Cell Line, Tumor
Cell Survival
/ drug effects
Drug Evaluation, Preclinical
Flavonoids
/ pharmacology
Humans
Mice
Neuroprotective Agents
/ pharmacology
Propiophenones
/ pharmacology
Protein Aggregation, Pathological
/ drug therapy
Random Allocation
Reactive Oxygen Species
/ metabolism
Derivatives of xanthohumol
amyloid aggregation inhibition
blood-brain barrier permeable
neuroprotective.
Journal
Current Alzheimer research
ISSN: 1875-5828
Titre abrégé: Curr Alzheimer Res
Pays: United Arab Emirates
ID NLM: 101208441
Informations de publication
Date de publication:
2019
2019
Historique:
received:
28
12
2018
revised:
09
08
2019
accepted:
21
08
2019
pubmed:
28
8
2019
medline:
4
9
2020
entrez:
28
8
2019
Statut:
ppublish
Résumé
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). 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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31453789
pii: CAR-EPUB-100466
doi: 10.2174/1567205016666190827123222
doi:
Substances chimiques
Amyloid beta-Peptides
0
Flavonoids
0
Neuroprotective Agents
0
Propiophenones
0
Reactive Oxygen Species
0
Calcium
SY7Q814VUP
xanthohumol
T4467YT1NT
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
836-842Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.