The Prenylflavonoid xanthohumol reduces Alzheimer-Like changes and modulates multiple pathogenic molecular pathways in the Neuro2a/APPswe cell model of AD

Xianfeng Huang, Jing Wang, Xiao Chen, Pan Liu, Shujin Wang, Fangchen Song, Zaijun Zhang, Feiqi Zhu, Xinfeng Huang, Jianjun Liu, Guoqiang Song, Peter Spencer, Xifei Yang

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.

Original languageEnglish (US)
Article number199
JournalFrontiers in Pharmacology
Volume9
Issue numberAPR
DOIs
StatePublished - Apr 4 2018

Fingerprint

Alzheimer Disease
Proteins
Humulus
Endoplasmic Reticulum Stress
Proteasome Endopeptidase Complex
Heat-Shock Proteins
Cytoskeleton
Neurodegenerative Diseases
Oxidative Stress
Western Blotting
Two-Dimensional Difference Gel Electrophoresis
Biological Phenomena
Molecular Chaperones
xanthohumol
HEK293 Cells
Mutant Proteins
Neuroblastoma
Amyloid
Proteomics
Adenosine Triphosphatases

Keywords

  • Alzheimer's disease (AD)
  • Amyloid-β (Aβ)
  • Cytoskeleton
  • Endoplasmic reticulum (ER) stress
  • Oxidative stress
  • Xanthohumol (Xn)

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

The Prenylflavonoid xanthohumol reduces Alzheimer-Like changes and modulates multiple pathogenic molecular pathways in the Neuro2a/APPswe cell model of AD. / Huang, Xianfeng; Wang, Jing; Chen, Xiao; Liu, Pan; Wang, Shujin; Song, Fangchen; Zhang, Zaijun; Zhu, Feiqi; Huang, Xinfeng; Liu, Jianjun; Song, Guoqiang; Spencer, Peter; Yang, Xifei.

In: Frontiers in Pharmacology, Vol. 9, No. APR, 199, 04.04.2018.

Research output: Contribution to journalArticle

Huang, Xianfeng ; Wang, Jing ; Chen, Xiao ; Liu, Pan ; Wang, Shujin ; Song, Fangchen ; Zhang, Zaijun ; Zhu, Feiqi ; Huang, Xinfeng ; Liu, Jianjun ; Song, Guoqiang ; Spencer, Peter ; Yang, Xifei. / The Prenylflavonoid xanthohumol reduces Alzheimer-Like changes and modulates multiple pathogenic molecular pathways in the Neuro2a/APPswe cell model of AD. In: Frontiers in Pharmacology. 2018 ; Vol. 9, No. APR.
@article{6eefc5fe03e5436f94ac315ca0bac7e7,
title = "The Prenylflavonoid xanthohumol reduces Alzheimer-Like changes and modulates multiple pathogenic molecular pathways in the Neuro2a/APPswe cell model of AD",
abstract = "Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.",
keywords = "Alzheimer's disease (AD), Amyloid-β (Aβ), Cytoskeleton, Endoplasmic reticulum (ER) stress, Oxidative stress, Xanthohumol (Xn)",
author = "Xianfeng Huang and Jing Wang and Xiao Chen and Pan Liu and Shujin Wang and Fangchen Song and Zaijun Zhang and Feiqi Zhu and Xinfeng Huang and Jianjun Liu and Guoqiang Song and Peter Spencer and Xifei Yang",
year = "2018",
month = "4",
day = "4",
doi = "10.3389/fphar.2018.00199",
language = "English (US)",
volume = "9",
journal = "Frontiers in Pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S. A.",
number = "APR",

}

TY - JOUR

T1 - The Prenylflavonoid xanthohumol reduces Alzheimer-Like changes and modulates multiple pathogenic molecular pathways in the Neuro2a/APPswe cell model of AD

AU - Huang, Xianfeng

AU - Wang, Jing

AU - Chen, Xiao

AU - Liu, Pan

AU - Wang, Shujin

AU - Song, Fangchen

AU - Zhang, Zaijun

AU - Zhu, Feiqi

AU - Huang, Xinfeng

AU - Liu, Jianjun

AU - Song, Guoqiang

AU - Spencer, Peter

AU - Yang, Xifei

PY - 2018/4/4

Y1 - 2018/4/4

N2 - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.

AB - Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has proved refractory to drug treatment. Given evidence of neuroprotection in animal models of ischemic stroke, we assessed the prenylflavonoid xanthohumol from the Common Hop (Humulus lupulus L.) for therapeutic potential in murine neuroblastoma N2a cells stably expressing human Swedish mutant amyloid precursor protein (N2a/APP), a well-characterized cellular model of AD. The ELISA and Western-blot analysis revealed that xanthohumol (Xn) inhibited Aβ accumulation and APP processing, and that Xn ameliorated tau hyperphosphorylation via PP2A, GSK3β pathways in N2a/APP cells. The amelioration of tau hyperphosphorylation by Xn was also validated on HEK293/Tau cells, another cell line with tau hyperphosphorylation. Proteomic analysis (2D-DIGE-coupled MS) revealed a total of 30 differentially expressed lysate proteins in N2a/APP vs. wild-type (WT) N2a cells (N2a/WT), and a total of 21 differentially expressed proteins in lysates of N2a/APP cells in the presence or absence of Xn. Generally, these 51 differential proteins could be classified into seven main categories according to their functions, including: endoplasmic reticulum (ER) stress-associated proteins; oxidative stress-associated proteins; proteasome-associated proteins; ATPase and metabolism-associated proteins; cytoskeleton-associated proteins; molecular chaperones-associated proteins, and others. We used Western-blot analysis to validate Xn-associated changes of some key proteins in several biological/pathogenic processes. Taken together, we show that Xn reduces AD-related changes in stably transfected N2a/APP cells. The underlying mechanisms involve modulation of multiple pathogenic pathways, including those involved in ER stress, oxidative stress, proteasome molecular systems, and the neuronal cytoskeleton. These results suggest Xn may have potential for the treatment of AD and/or neuropathologically related neurodegenerative diseases.

KW - Alzheimer's disease (AD)

KW - Amyloid-β (Aβ)

KW - Cytoskeleton

KW - Endoplasmic reticulum (ER) stress

KW - Oxidative stress

KW - Xanthohumol (Xn)

UR - http://www.scopus.com/inward/record.url?scp=85045027226&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045027226&partnerID=8YFLogxK

U2 - 10.3389/fphar.2018.00199

DO - 10.3389/fphar.2018.00199

M3 - Article

AN - SCOPUS:85045027226

VL - 9

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

SN - 1663-9812

IS - APR

M1 - 199

ER -