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, RCC1 2
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
2011 Impact Factor: 2.105
2011 SCImago Journal Rankings: 0.163
DOIhttp://dx.doi.org/10.1016/j.neulet.2009.12.028
ReferencesReferences in Scopus
GrantsInstitute of molecular technology for drug discovery and synthesis
DC Field
Value
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.grantInstitute of molecular technology for drug discovery and synthesis
dc.description.grantcode8708
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
2011 Impact Factor: 2.105
2011 SCImago Journal Rankings: 0.163
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.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
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