Article: Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
| Title | Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Chao, J1 2 Li, H2 Cheng, KW2 Yu, MS1 Chang, RCC1 2 Wang, M2 | ||||||
| Keywords | 6-Hydroxydopamine Neuroprotection Parkinson's disease Pinostilbene Resveratrol | ||||||
| Issue Date | 2010 | ||||||
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio | ||||||
| Citation | Journal 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 | ||||||
| Abstract | Resveratrol (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. | ||||||
| ISSN | 0955-2863 2011 Impact Factor: 3.891 2011 SCImago Journal Rankings: 0.233 | ||||||
| DOI | http://dx.doi.org/10.1016/j.jnutbio.2009.02.004 | ||||||
| ISI Accession Number ID | WOS:000278149400004
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. | ||||||
| References | References in Scopus | ||||||
| Grants | Investigating the impact of oligomeric \xE1-amyloid peptide on RNA-trifficking in neurons. Implication on local protein translation control in neurons. |
| dc.contributor.author | Chao, J | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Li, H | ||||||
| dc.contributor.author | Cheng, KW | ||||||
| dc.contributor.author | Yu, MS | ||||||
| dc.contributor.author | Chang, RCC | ||||||
| dc.contributor.author | Wang, M | ||||||
| dc.date.accessioned | 2012-06-26T05:57:54Z | ||||||
| dc.date.available | 2012-06-26T05:57:54Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.abstract | Resveratrol (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.grant | Investigating the impact of oligomeric \xE1-amyloid peptide on RNA-trifficking in neurons. Implication on local protein translation control in neurons. | ||||||
| dc.description.grantcode | 97843 | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Journal 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.citeulike | 5368446 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.jnutbio.2009.02.004 | ||||||
| dc.identifier.epage | 489 | ||||||
| dc.identifier.hkuros | 170232 | ||||||
| dc.identifier.isi | WOS:000278149400004
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.issn | 0955-2863 2011 Impact Factor: 3.891 2011 SCImago Journal Rankings: 0.233 | ||||||
| dc.identifier.issue | 6 | ||||||
| dc.identifier.pmid | 19443200 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77952882393 | ||||||
| dc.identifier.spage | 482 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/149743 | ||||||
| dc.identifier.volume | 21 | ||||||
| dc.language | eng | ||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Journal of Nutritional Biochemistry | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | The Journal of Nutritional Biochemistry. Copyright © Elsevier Inc. | ||||||
| dc.subject.mesh | Caspase 3 - Metabolism | ||||||
| dc.subject.mesh | Cell Line, Tumor | ||||||
| dc.subject.mesh | Cells, Cultured | ||||||
| dc.subject.mesh | Dose-Response Relationship, Drug | ||||||
| dc.subject.mesh | Free Radical Scavengers - Metabolism | ||||||
| dc.subject.mesh | Humans | ||||||
| dc.subject.mesh | L-Lactate Dehydrogenase - Metabolism | ||||||
| dc.subject.mesh | Methylation | ||||||
| dc.subject.mesh | Models, Chemical | ||||||
| dc.subject.mesh | Neurons - Drug Effects - Metabolism | ||||||
| dc.subject.mesh | Neurotoxins - Metabolism | ||||||
| dc.subject.mesh | Oxidopamine - Pharmacology | ||||||
| dc.subject.mesh | Phosphorylation | ||||||
| dc.subject.mesh | Stilbenes - Chemistry - Pharmacology | ||||||
| dc.subject | 6-Hydroxydopamine | ||||||
| dc.subject | Neuroprotection | ||||||
| dc.subject | Parkinson's disease | ||||||
| dc.subject | Pinostilbene | ||||||
| dc.subject | Resveratrol | ||||||
| dc.title | Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong Li Ka Shing Faculty of Medicine
- The University of Hong Kong