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Article: A pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
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TitleA pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
 
AuthorsChao, J2
Lau, WKW2
Huie, MJ2 3
Ho, YS2
Yu, MS2
Lai, CSW2
Wang, M2
Yuen, WH2
Lam, WH4
Chan, TH4
Chang, RCC2 1
 
Keywords6-Hydroxydopamine
Green tea polyphenols/EGCG
Neuroprotection
Prodrug/pEGCG
 
Issue Date2010
 
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neulet
 
CitationNeuroscience Letters, 2010, v. 469 n. 3, p. 360-364 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neulet.2009.12.028
 
AbstractRegular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 μM 6-hydroxydopamine (6-OHDA) for 24 h. We found that a broad dosage range of pEGCG (from 0.1 to 10 μM) could significantly reduce lactate dehydrogenase release. Likewise, 10 μM of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 μM of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 μM markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailbility for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future. © 2009 Elsevier Ireland Ltd. All rights reserved.
 
ISSN0304-3940
2012 Impact Factor: 2.026
2012 SCImago Journal Rankings: 0.815
 
DOIhttp://dx.doi.org/10.1016/j.neulet.2009.12.028
 
ISI Accession Number IDWOS:000274722100017
Funding AgencyGrant Number
HKU Strategic Research Theme on Drug Discovery
Area of Excellence on Institute of Molecular Technology for Drug Discovery and SynthesisAoE/P-10/01
Hong Kong Polytechnic University Area of Strategic Development Fund
Funding Information:

The study is supported by HKU Strategic Research Theme on Drug Discovery, Area of Excellence on Institute of Molecular Technology for Drug Discovery and Synthesis (AoE/P-10/01), and The Hong Kong Polytechnic University Area of Strategic Development Fund. YSH is supported by a postdoctoral fellowship.

 
ReferencesReferences in Scopus
 
GrantsInstitute of molecular technology for drug discovery and synthesis
 
DC FieldValue
dc.contributor.authorChao, J
 
dc.contributor.authorLau, WKW
 
dc.contributor.authorHuie, MJ
 
dc.contributor.authorHo, YS
 
dc.contributor.authorYu, MS
 
dc.contributor.authorLai, CSW
 
dc.contributor.authorWang, M
 
dc.contributor.authorYuen, WH
 
dc.contributor.authorLam, WH
 
dc.contributor.authorChan, TH
 
dc.contributor.authorChang, RCC
 
dc.date.accessioned2010-09-06T05:59:48Z
 
dc.date.available2010-09-06T05:59:48Z
 
dc.date.issued2010
 
dc.description.abstractRegular consumption of green tea benefits people in prevention from cardiovascular disorders, obesity as well as neurodegenerative diseases. (-)-Epigallocatechin-3-gallate (EGCG) is regarded as the most biologically active catechin in green tea. However, the stability and bioavailability of EGCG are restricted. The purpose of the present study was to investigate whether a pro-drug, a fully acetylated EGCG (pEGCG), could be more effective in neuroprotection in Parkinsonism mimic cellular model. Retinoic acid (RA)-differentiated neuroblastoma SH-SY5Y cells were pre-treated with different concentrations of EGCG and pEGCG for 30 min and followed by incubation of 25 μM 6-hydroxydopamine (6-OHDA) for 24 h. We found that a broad dosage range of pEGCG (from 0.1 to 10 μM) could significantly reduce lactate dehydrogenase release. Likewise, 10 μM of pEGCG was effective in reducing caspase-3 activity, while EGCG at all concentrations tested in the model failed to attenuate caspase-3 activity induced by 6-OHDA. Furthermore, Western-blot analysis showed that Akt could be one of the specific signaling pathways stimulated by pEGCG in neuroprotection. It was demonstrated that 25 μM of 6-OHDA significantly suppressed the phosphorylation level of Akt. Only pEGCG at 10 μM markedly increased its phosphorylation level compared to 6-OHDA alone. Taken together, as pEGCG has higher stability and bioavailbility for further investigation, it could be a potential neuroprotective agent and our current findings may offer certain clues for optimizing its application in future. © 2009 Elsevier Ireland Ltd. All rights reserved.
 
dc.description.naturepostprint
 
dc.identifier.citationNeuroscience Letters, 2010, v. 469 n. 3, p. 360-364 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neulet.2009.12.028
 
dc.identifier.citeulike6476727
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.neulet.2009.12.028
 
dc.identifier.epage364
 
dc.identifier.hkuros169237
 
dc.identifier.isiWOS:000274722100017
Funding AgencyGrant Number
HKU Strategic Research Theme on Drug Discovery
Area of Excellence on Institute of Molecular Technology for Drug Discovery and SynthesisAoE/P-10/01
Hong Kong Polytechnic University Area of Strategic Development Fund
Funding Information:

The study is supported by HKU Strategic Research Theme on Drug Discovery, Area of Excellence on Institute of Molecular Technology for Drug Discovery and Synthesis (AoE/P-10/01), and The Hong Kong Polytechnic University Area of Strategic Development Fund. YSH is supported by a postdoctoral fellowship.

 
dc.identifier.issn0304-3940
2012 Impact Factor: 2.026
2012 SCImago Journal Rankings: 0.815
 
dc.identifier.issue3
 
dc.identifier.openurl
 
dc.identifier.pmid20026175
 
dc.identifier.scopuseid_2-s2.0-73849147183
 
dc.identifier.spage360
 
dc.identifier.urihttp://hdl.handle.net/10722/67956
 
dc.identifier.volume469
 
dc.languageeng
 
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neulet
 
dc.publisher.placeIreland
 
dc.relation.ispartofNeuroscience Letters
 
dc.relation.projectInstitute of molecular technology for drug discovery and synthesis
 
dc.relation.referencesReferences in Scopus
 
dc.rightsNeuroscience Letters. Copyright © Elsevier Ireland Ltd.
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject.meshCatechin - administration and dosage - analogs and derivatives - chemistry - pharmacology
 
dc.subject.meshCentral Nervous System Agents - administration and dosage - toxicity
 
dc.subject.meshNeurons - cytology - drug effects - metabolism
 
dc.subject.meshNeuroprotective Agents - administration and dosage - chemistry - pharmacology
 
dc.subject.meshOxidopamine - administration and dosage - toxicity
 
dc.subject6-Hydroxydopamine
 
dc.subjectGreen tea polyphenols/EGCG
 
dc.subjectNeuroprotection
 
dc.subjectProdrug/pEGCG
 
dc.titleA pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. The University of Hong Kong
  3. University of Calgary
  4. Hong Kong Polytechnic University