TY - JOUR
T1 - Amyloid-β aggregation inhibitory and neuroprotective effects of xanthohumol and its derivatives for Alzheimer’s disease
AU - Wang, Xueli
AU - Ho, See Lok
AU - Poon, Chung Yan
AU - Yan, Ting
AU - LI, Hung Wing
AU - WONG, Ricky M S
N1 - Funding Information:
This work was supported by the National Natural Sciences Foundation of China (no. 21675135). We are also thankful for the support of the Collaborative Research Fund of the Hong Kong Research Grant Council (C2012-15G).
Funding Information:
We are also thankful for the support of the Collaborative Research Fund of the Hong Kong Research Grant Council (C2012-15G).
Funding Information:
This work was supported by the National ences Foundation of China (no. 21675135).
PY - 2019/8/27
Y1 - 2019/8/27
N2 - 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.
AB - 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.
KW - Amyloid aggregation inhibition
KW - Blood-brain barrier permeable
KW - Derivatives of xanthohumol
KW - Neuroprotective
UR - http://www.scopus.com/inward/record.url?scp=85075089626&partnerID=8YFLogxK
U2 - 10.2174/1567205016666190827123222
DO - 10.2174/1567205016666190827123222
M3 - Article
C2 - 31453789
AN - SCOPUS:85075089626
VL - 16
SP - 836
EP - 842
JO - Current Alzheimer Research
JF - Current Alzheimer Research
SN - 1567-2050
IS - 9
ER -