Article: Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model

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TitleBerberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model
AuthorsDurairajan, SSK2
Liu, LF2
Lu, JH2
Chen, LL2
Yuan, Q4
Chung, SK1
Huang, L3
Li, XS3
Huang, JD1
Li, M2
KeywordsΒ-Amyloid
Alzheimer's Disease
Amyloid Precursor Protein
Berberine
Glycogen Synthase Kinase
Tau Phosphorylation
Tgcrnd8 Mice
Issue Date2012
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/neuaging
CitationNeurobiology Of Aging, 2012, v. 33 n. 12, p 2903-2919 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016
AbstractThe accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted. © 2012 Elsevier Inc. All rights reserved.
ISSN0197-4580
2011 Impact Factor: 6.189
2011 SCImago Journal Rankings: 0.391
DOIhttp://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016
DC Field
Value
dc.contributor.authorDurairajan, SSK
dc.contributor.authorLiu, LF
dc.contributor.authorLu, JH
dc.contributor.authorChen, LL
dc.contributor.authorYuan, Q
dc.contributor.authorChung, SK
dc.contributor.authorHuang, L
dc.contributor.authorLi, XS
dc.contributor.authorHuang, JD
dc.contributor.authorLi, M
dc.date.accessioned2012-06-26T05:58:37Z
dc.date.available2012-06-26T05:58:37Z
dc.date.issued2012
dc.description.abstractThe accumulation of β-amyloid (Aβ) peptide derived from abnormal processing of amyloid precursor protein (APP) is a common pathological hallmark of Alzheimer's disease (AD) brains. In this study, we evaluated the therapeutic effect of berberine (BBR) extracted from Coptis chinensis Franch, a Chinese medicinal herb, on the neuropathology and cognitive impairment in TgCRND8 mice, a well established transgenic mouse model of AD. Two-month-old TgCRND8 mice received a low (25 mg/kg per day) or a high dose of BBR (100 mg/kg per day) by oral gavage until 6 months old. BBR treatment significantly ameliorated learning deficits, long-term spatial memory retention, as well as plaque load compared with vehicle control treatment. In addition, enzyme-linked immunosorbent assay (ELISA) measurement showed that there was a profound reduction in levels of detergent-soluble and -insoluble β-amyloid in brain homogenates of BBR-treated mice. Glycogen synthase kinase (GSK)3, a major kinase involved in APP and tau phosphorylation, was significantly inhibited by BBR treatment. We also found that BBR significantly decreased the levels of C-terminal fragments of APP and the hyperphosphorylation of APP and tau via the Akt/glycogen synthase kinase 3 signaling pathway in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a-SwedAPP). Our results suggest that BBR provides neuroprotective effects in TgCRND8 mice through regulating APP processing and that further investigation of the BBR for therapeutic use in treating AD is warranted. © 2012 Elsevier Inc. All rights reserved.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNeurobiology Of Aging, 2012, v. 33 n. 12, p 2903-2919 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016
dc.identifier.citeulike11522637
dc.identifier.doihttp://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016
dc.identifier.hkuros199688
dc.identifier.issn0197-4580
2011 Impact Factor: 6.189
2011 SCImago Journal Rankings: 0.391
dc.identifier.scopuseid_2-s2.0-84866744899
dc.identifier.urihttp://hdl.handle.net/10722/149785
dc.languageeng
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/neuaging
dc.publisher.placeUnited States
dc.relation.ispartofNeurobiology of Aging
dc.subjectΒ-Amyloid
dc.subjectAlzheimer's Disease
dc.subjectAmyloid Precursor Protein
dc.subjectBerberine
dc.subjectGlycogen Synthase Kinase
dc.subjectTau Phosphorylation
dc.subjectTgcrnd8 Mice
dc.titleBerberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer's disease transgenic mouse model
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hong Kong Baptist University
  3. Sun Yat-Sen University
  4. Chinese University of Hong Kong