Cargando…

Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use mo...

Descripción completa

Detalles Bibliográficos
Autores principales: Zeng, Yue-Qin, Cui, Yin-Bo, Gu, Juan-Hua, Liang, Chen, Zhou, Xin-Fu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017345/
https://www.ncbi.nlm.nih.gov/pubmed/29642616
http://dx.doi.org/10.3390/molecules23040869
_version_ 1783334728157364224
author Zeng, Yue-Qin
Cui, Yin-Bo
Gu, Juan-Hua
Liang, Chen
Zhou, Xin-Fu
author_facet Zeng, Yue-Qin
Cui, Yin-Bo
Gu, Juan-Hua
Liang, Chen
Zhou, Xin-Fu
author_sort Zeng, Yue-Qin
collection PubMed
description Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.
format Online
Article
Text
id pubmed-6017345
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-60173452018-11-13 Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice Zeng, Yue-Qin Cui, Yin-Bo Gu, Juan-Hua Liang, Chen Zhou, Xin-Fu Molecules Article Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) within extracellular spaces of the brain. Aggregation of Aβ has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aβ amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aβ42, efficiently inhibits oligomerization as well as fibril formation and reduces Aβ oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aβ levels in the brain and plasma, decreases Aβ plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology. MDPI 2018-04-10 /pmc/articles/PMC6017345/ /pubmed/29642616 http://dx.doi.org/10.3390/molecules23040869 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zeng, Yue-Qin
Cui, Yin-Bo
Gu, Juan-Hua
Liang, Chen
Zhou, Xin-Fu
Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title_full Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title_fullStr Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title_full_unstemmed Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title_short Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice
title_sort scutellarin mitigates aβ-induced neurotoxicity and improves behavior impairments in ad mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017345/
https://www.ncbi.nlm.nih.gov/pubmed/29642616
http://dx.doi.org/10.3390/molecules23040869
work_keys_str_mv AT zengyueqin scutellarinmitigatesabinducedneurotoxicityandimprovesbehaviorimpairmentsinadmice
AT cuiyinbo scutellarinmitigatesabinducedneurotoxicityandimprovesbehaviorimpairmentsinadmice
AT gujuanhua scutellarinmitigatesabinducedneurotoxicityandimprovesbehaviorimpairmentsinadmice
AT liangchen scutellarinmitigatesabinducedneurotoxicityandimprovesbehaviorimpairmentsinadmice
AT zhouxinfu scutellarinmitigatesabinducedneurotoxicityandimprovesbehaviorimpairmentsinadmice