Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression

Publication type:
Journal article
Metadata:
Autoren
  • Florian Schuck
  • Ulrich Schmitt
  • Sven Reinhardt
  • Christian Freese
  • Ik-Soo Lee
  • Eckhard Thines
  • Thomas Efferth
  • Kristina Endres
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000362801400008&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2015.08.001
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: CT4TY
  • PubMed Identifier: 26407945
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Medicinal plant extracts
  • ADAM10
  • Caragana sinica
  • Alzheimer's disease
  • Blood-brain barrier
  • Alpha-viniferin
Paginierung
1027 - 1036
Datum der Veröffentlichung
2015
Status
Published
Titel
Extract of <i>Caragana sinica</i> as a potential therapeutic option for increasing alpha-secretase gene expression
Sub types
  • Article
Ausgabe der Zeitschrift
22

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Florian Schuck
  • Ulrich Schmitt
  • Sven Reinhardt
  • Christian Freese
  • Ik-Soo Lee
  • Eckhard Thines
  • Thomas Efferth
  • Kristina Endres
DOI
10.1016/j.phymed.2015.08.001
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
1027 - 1036
Datum der Veröffentlichung
2015
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2015.08.001
Datum der Datenerfassung
2019
Titel
Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression
Ausgabe der Zeitschrift
22

Data source: Crossref

Abstract
<h4>Background</h4>Alzheimer's disease represents one of the main neurological disorders in the aging population. Treatment options so far are only of symptomatic nature and efforts in developing disease modifying drugs by targeting amyloid beta peptide-generating enzymes remain fruitless in the majority of human studies. During the last years, an alternative approach emerged to target the physiological alpha-secretase ADAM10, which is not only able to prevent formation of toxic amyloid beta peptides but also provides a neuroprotective fragment of the amyloid precursor protein - sAPPalpha.<h4>Purpose</h4>To identify novel alpha-secretase enhancers from a library of 313 extracts of medicinal plants indigenous to Korea, a screening approach was used and hits were further evaluated for their therapeutic value.<h4>Methods</h4>The extract library was screened for selective enhancers of ADAM10 gene expression using a luciferase-based promoter reporter gene assay in the human neuroblastoma cell line SH-SY5Y. Candidate extracts were then tested in wild type mice for acute behavioral effects using an open field paradigm. Brain and liver tissue from treated mice was biochemically analyzed for ADAM10 gene expression in vivo. An in vitro blood-brain barrier model and an in vitro ATPase assay were used to unravel transport properties of bioactive compounds from extract candidates. Finally, fractionation of the most promising extract was performed to identify biologically active components.<h4>Results</h4>The extract of Caragana sinica (Buc'hoz) Rehder was identified as the best candidate from our screening approach. We were able to demonstrate that the extract is acutely applicable in mice without obvious side effects and induces ADAM10 gene expression in peripheral tissue. A hindered passage across the blood-brain barrier was detected explaining lack of cerebral induction of ADAM10 gene expression in treated mice. By fractionating C. sinica extract we identified alpha-viniferin as one of the biologically active components.<h4>Conclusion</h4>The extract of C. sinica and alpha-viniferin as one of its bioactive constituents might serve as novel therapeutic options for treating Alzheimer's disease by increasing ADAM10 gene expression. The identification of alpha-viniferin represents a promising starting point to achieve blood-brain barrier penetrance in the future.
Addresses
  • Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University, Untere Zahlbacher Strasse 8, 55131 Mainz, Germany.
Autoren
DOI
10.1016/j.phymed.2015.08.001
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 26407945
Open access
false
ISSN
0944-7113
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Blood-Brain Barrier
  • Cell Line, Tumor
  • Animals
  • Mice, Knockout
  • Humans
  • Mice
  • Caragana
  • Plants, Medicinal
  • Benzofurans
  • Amyloid beta-Protein Precursor
  • Membrane Proteins
  • Plant Extracts
  • Gene Expression Regulation, Enzymologic
  • Male
  • ADAM Proteins
  • Amyloid Precursor Protein Secretases
  • Promoter Regions, Genetic
  • Aspartic Acid Endopeptidases
  • ADAM10 Protein
Sprache
eng
Medium
Print-Electronic
Online publication date
2015
Paginierung
1027 - 1036
Datum der Veröffentlichung
2015
Status
Published
Datum der Datenerfassung
2015
Titel
Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
22

Data source: Europe PubMed Central

Abstract
BACKGROUND: Alzheimer's disease represents one of the main neurological disorders in the aging population. Treatment options so far are only of symptomatic nature and efforts in developing disease modifying drugs by targeting amyloid beta peptide-generating enzymes remain fruitless in the majority of human studies. During the last years, an alternative approach emerged to target the physiological alpha-secretase ADAM10, which is not only able to prevent formation of toxic amyloid beta peptides but also provides a neuroprotective fragment of the amyloid precursor protein - sAPPalpha. PURPOSE: To identify novel alpha-secretase enhancers from a library of 313 extracts of medicinal plants indigenous to Korea, a screening approach was used and hits were further evaluated for their therapeutic value. METHODS: The extract library was screened for selective enhancers of ADAM10 gene expression using a luciferase-based promoter reporter gene assay in the human neuroblastoma cell line SH-SY5Y. Candidate extracts were then tested in wild type mice for acute behavioral effects using an open field paradigm. Brain and liver tissue from treated mice was biochemically analyzed for ADAM10 gene expression in vivo. An in vitro blood-brain barrier model and an in vitro ATPase assay were used to unravel transport properties of bioactive compounds from extract candidates. Finally, fractionation of the most promising extract was performed to identify biologically active components. RESULTS: The extract of Caragana sinica (Buc'hoz) Rehder was identified as the best candidate from our screening approach. We were able to demonstrate that the extract is acutely applicable in mice without obvious side effects and induces ADAM10 gene expression in peripheral tissue. A hindered passage across the blood-brain barrier was detected explaining lack of cerebral induction of ADAM10 gene expression in treated mice. By fractionating C. sinica extract we identified alpha-viniferin as one of the biologically active components. CONCLUSION: The extract of C. sinica and alpha-viniferin as one of its bioactive constituents might serve as novel therapeutic options for treating Alzheimer's disease by increasing ADAM10 gene expression. The identification of alpha-viniferin represents a promising starting point to achieve blood-brain barrier penetrance in the future.
Date of acceptance
2015
Autoren
  • Florian Schuck
  • Ulrich Schmitt
  • Sven Reinhardt
  • Christian Freese
  • Ik-Soo Lee
  • Eckhard Thines
  • Thomas Efferth
  • Kristina Endres
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26407945
DOI
10.1016/j.phymed.2015.08.001
eISSN
1618-095X
Ausgabe der Veröffentlichung
11
Zeitschrift
Phytomedicine
Schlüsselwörter
  • ADAM10
  • Alpha-viniferin
  • Alzheimer's disease
  • Blood–brain barrier
  • Caragana sinica
  • Medicinal plant extracts
  • ADAM Proteins
  • ADAM10 Protein
  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor
  • Animals
  • Aspartic Acid Endopeptidases
  • Benzofurans
  • Blood-Brain Barrier
  • Caragana
  • Cell Line, Tumor
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Plant Extracts
  • Plants, Medicinal
  • Promoter Regions, Genetic
Sprache
eng
Country
Germany
Paginierung
1027 - 1036
PII
S0944-7113(15)00235-4
Datum der Veröffentlichung
2015
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2015
Titel
Extract of Caragana sinica as a potential therapeutic option for increasing alpha-secretase gene expression.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
22

Data source: PubMed

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