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Article: Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
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TitleProtective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
 
AuthorsChao, J2 1
Li, H2
Cheng, KW2
Yu, MS1
Chang, RCC1 2
Wang, M2
 
Keywords6-Hydroxydopamine
Neuroprotection
Parkinson's disease
Pinostilbene
Resveratrol
 
Issue Date2010
 
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio
 
CitationJournal Of Nutritional Biochemistry, 2010, v. 21 n. 6, p. 482-489 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.jnutbio.2009.02.004
 
AbstractResveratrol (3,4',5-trans-trihydroxystilbene) is a phytoalexin with emerging lines of evidence supporting its beneficial effects on cardiovascular systems and inhibition of carcinogenesis. It has also been reported that certain methylated resveratrol derivatives are more effective than resveratrol in the prevention/treatment of cancer. However, little is known about the impact of resveratrol and its derivatives on the development of Parkinson's disease. In this study, we compared the neuroprotective effects of resveratrol with four methylated (fully or partially) resveratrol derivatives against parkinsonian mimetic 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells. Release of lactate dehydrogenase and activity of caspase-3 triggered by 6-OHDA were significantly reduced by resveratrol and one of the methylated derivatives, pinostilbene (3,4'-dihydroxy-5-methoxystilbene), in a dose-dependent manner. In addition, pinostilbene exerted a potent neuroprotective effect with a wider effective concentration range than resveratrol. By using high-performance liquid chromatography, we found that uptake of pinostilbene into SH-SY5Y cells was significantly higher than that of resveratrol. Enhanced bioavailability may thus be a major factor contributing to the neuroprotective activity of pinostilbene. Moreover, Western blot analysis demonstrated that pinostilbene markedly attenuated the phosphorylation of JNK and c-Jun triggered by 6-OHDA. Besides, mammalian target of rapamycin kinase may be an intracellular target accounting for the neuroprotective effects of pinostilbene. Our findings demonstrate the potential of methylated stilbenes in neuroprotection and provide important information for further research in this field. © 2010 Elsevier Inc.
 
ISSN0955-2863
2013 Impact Factor: 4.592
2013 SCImago Journal Rankings: 1.627
 
DOIhttp://dx.doi.org/10.1016/j.jnutbio.2009.02.004
 
ISI Accession Number IDWOS:000278149400004
Funding AgencyGrant Number
HKU200711159028
University of Hong Kong
Funding Information:

The study is supported by HKU Strategic Theme Research on Drug Discovery, HKU Seed Funding for Basic Research (200711159028) to R. C.-C.C. J.C., HI. and K.-W.C. are supported by a postgraduate studentship, and M.-S.Y. is supported by a postdoctoral fellowship from the University of Hong Kong.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorChao, J
 
dc.contributor.authorLi, H
 
dc.contributor.authorCheng, KW
 
dc.contributor.authorYu, MS
 
dc.contributor.authorChang, RCC
 
dc.contributor.authorWang, M
 
dc.date.accessioned2012-06-26T05:57:54Z
 
dc.date.available2012-06-26T05:57:54Z
 
dc.date.issued2010
 
dc.description.abstractResveratrol (3,4',5-trans-trihydroxystilbene) is a phytoalexin with emerging lines of evidence supporting its beneficial effects on cardiovascular systems and inhibition of carcinogenesis. It has also been reported that certain methylated resveratrol derivatives are more effective than resveratrol in the prevention/treatment of cancer. However, little is known about the impact of resveratrol and its derivatives on the development of Parkinson's disease. In this study, we compared the neuroprotective effects of resveratrol with four methylated (fully or partially) resveratrol derivatives against parkinsonian mimetic 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in SH-SY5Y cells. Release of lactate dehydrogenase and activity of caspase-3 triggered by 6-OHDA were significantly reduced by resveratrol and one of the methylated derivatives, pinostilbene (3,4'-dihydroxy-5-methoxystilbene), in a dose-dependent manner. In addition, pinostilbene exerted a potent neuroprotective effect with a wider effective concentration range than resveratrol. By using high-performance liquid chromatography, we found that uptake of pinostilbene into SH-SY5Y cells was significantly higher than that of resveratrol. Enhanced bioavailability may thus be a major factor contributing to the neuroprotective activity of pinostilbene. Moreover, Western blot analysis demonstrated that pinostilbene markedly attenuated the phosphorylation of JNK and c-Jun triggered by 6-OHDA. Besides, mammalian target of rapamycin kinase may be an intracellular target accounting for the neuroprotective effects of pinostilbene. Our findings demonstrate the potential of methylated stilbenes in neuroprotection and provide important information for further research in this field. © 2010 Elsevier Inc.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationJournal Of Nutritional Biochemistry, 2010, v. 21 n. 6, p. 482-489 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.jnutbio.2009.02.004
 
dc.identifier.citeulike5368446
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.jnutbio.2009.02.004
 
dc.identifier.epage489
 
dc.identifier.hkuros170232
 
dc.identifier.isiWOS:000278149400004
Funding AgencyGrant Number
HKU200711159028
University of Hong Kong
Funding Information:

The study is supported by HKU Strategic Theme Research on Drug Discovery, HKU Seed Funding for Basic Research (200711159028) to R. C.-C.C. J.C., HI. and K.-W.C. are supported by a postgraduate studentship, and M.-S.Y. is supported by a postdoctoral fellowship from the University of Hong Kong.

 
dc.identifier.issn0955-2863
2013 Impact Factor: 4.592
2013 SCImago Journal Rankings: 1.627
 
dc.identifier.issue6
 
dc.identifier.pmid19443200
 
dc.identifier.scopuseid_2-s2.0-77952882393
 
dc.identifier.spage482
 
dc.identifier.urihttp://hdl.handle.net/10722/149743
 
dc.identifier.volume21
 
dc.languageeng
 
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of Nutritional Biochemistry
 
dc.relation.referencesReferences in Scopus
 
dc.rightsThe Journal of Nutritional Biochemistry. Copyright © Elsevier Inc.
 
dc.subject.meshCaspase 3 - Metabolism
 
dc.subject.meshCell Line, Tumor
 
dc.subject.meshCells, Cultured
 
dc.subject.meshDose-Response Relationship, Drug
 
dc.subject.meshFree Radical Scavengers - Metabolism
 
dc.subject.meshHumans
 
dc.subject.meshL-Lactate Dehydrogenase - Metabolism
 
dc.subject.meshMethylation
 
dc.subject.meshModels, Chemical
 
dc.subject.meshNeurons - Drug Effects - Metabolism
 
dc.subject.meshNeurotoxins - Metabolism
 
dc.subject.meshOxidopamine - Pharmacology
 
dc.subject.meshPhosphorylation
 
dc.subject.meshStilbenes - Chemistry - Pharmacology
 
dc.subject6-Hydroxydopamine
 
dc.subjectNeuroprotection
 
dc.subjectParkinson's disease
 
dc.subjectPinostilbene
 
dc.subjectResveratrol
 
dc.titleProtective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
 
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