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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

TitleA pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine
Authors
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
Citation
Neuroscience Letters, 2010, v. 469 n. 3, p. 360-364 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/67956
ISSN
2014 Impact Factor: 2.030
2014 SCImago Journal Rankings: 0.864
ISI Accession Number ID
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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorChao, Jen_HK
dc.contributor.authorLau, WKWen_HK
dc.contributor.authorHuie, MJen_HK
dc.contributor.authorHo, YSen_HK
dc.contributor.authorYu, MSen_HK
dc.contributor.authorLai, CSWen_HK
dc.contributor.authorWang, Men_HK
dc.contributor.authorYuen, WHen_HK
dc.contributor.authorLam, WHen_HK
dc.contributor.authorChan, THen_HK
dc.contributor.authorChang, RCCen_HK
dc.date.accessioned2010-09-06T05:59:48Z-
dc.date.available2010-09-06T05:59:48Z-
dc.date.issued2010en_HK
dc.identifier.citationNeuroscience Letters, 2010, v. 469 n. 3, p. 360-364en_HK
dc.identifier.issn0304-3940en_HK
dc.identifier.urihttp://hdl.handle.net/10722/67956-
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.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuleten_HK
dc.relation.ispartofNeuroscience Lettersen_HK
dc.rightsNeuroscience Letters. Copyright © Elsevier Ireland Ltd.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject6-Hydroxydopamineen_HK
dc.subjectGreen tea polyphenols/EGCGen_HK
dc.subjectNeuroprotectionen_HK
dc.subjectProdrug/pEGCGen_HK
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.titleA pro-drug of the green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamineen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0304-3940&volume=469&issue=3&spage=360&epage=364&date=2010&atitle=A+pro-drug+of+the+green+tea+polyphenol+(-)-epigallocatechin-3-gallate+(EGCG)+prevents+differentiated+SH-SY5Y+cells+from+toxicity+induced+by+6-hydroxydopamineen_HK
dc.identifier.emailWang, M: mfwang@hku.hken_HK
dc.identifier.emailChang, RCC: rccchang@hku.hken_HK
dc.identifier.authorityWang, M=rp00800en_HK
dc.identifier.authorityChang, RCC=rp00470en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.neulet.2009.12.028en_HK
dc.identifier.pmid20026175en_HK
dc.identifier.scopuseid_2-s2.0-73849147183en_HK
dc.identifier.hkuros169237en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73849147183&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume469en_HK
dc.identifier.issue3en_HK
dc.identifier.spage360en_HK
dc.identifier.epage364en_HK
dc.identifier.isiWOS:000274722100017-
dc.publisher.placeIrelanden_HK
dc.relation.projectInstitute of molecular technology for drug discovery and synthesis-
dc.identifier.scopusauthoridChao, J=24558959000en_HK
dc.identifier.scopusauthoridLau, WKW=35292424400en_HK
dc.identifier.scopusauthoridHuie, MJ=35867164800en_HK
dc.identifier.scopusauthoridHo, YS=14031513600en_HK
dc.identifier.scopusauthoridYu, MS=35346047600en_HK
dc.identifier.scopusauthoridLai, CSW=26022547000en_HK
dc.identifier.scopusauthoridWang, M=7406691844en_HK
dc.identifier.scopusauthoridYuen, WH=7102761282en_HK
dc.identifier.scopusauthoridLam, WH=26643561300en_HK
dc.identifier.scopusauthoridChan, TH=35291257900en_HK
dc.identifier.scopusauthoridChang, RCC=7403713410en_HK
dc.identifier.citeulike6476727-

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