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Disclosing the potential of eleganolone for Parkinson’s disease therapeutics: neuroprotective and anti-inflammatory activities

2021Journal article Restricted access
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dc.contributor.authorSilva, Joana
dc.contributor.authorAlves, Celso
dc.contributor.authorPinteus, Susete
dc.contributor.authorSusano, Patrícia
dc.contributor.authorSimões, Marco
dc.contributor.authorGuedes, Miguel
dc.contributor.authorMartins, Alice
dc.contributor.authorRehfeldt, Stephanie
dc.contributor.authorGaspar, Helena
dc.contributor.authorGoettert, Márcia Inês
dc.contributor.authorAlfonso, Amparo
dc.contributor.authorPedrosa, Rui
dc.date.accessioned2021-08-03T14:19:56Z
dc.date.available2021-08-03T14:19:56Z
dc.date.issued2021
dc.descriptionFCT is also acknowledged for the grant attributed to Joana Silva (SFRH/BD/103255/2014). This work was supported by the Portuguese Foundation for Science and Technology (FCT) through the strategic project UID/04292/2020 grant to MARE—Marine and Environmental Sciences Centre and UIDP/ 04046/2020 and UIDB/04046/2020 granted to BioISI—BioSystems and Integrative Sciences Institute, through POINT4PAC project (Oncologia de Precisao: Terapias e Tecnologias Inovadoras (SAICTPAC/0019/ 2015-LISBOA- 01–0145-FEDER-016405)), through CROSS-ATLANTIC project (PTDC/BIA-OUT/29250/2017), co-financed by COMPETE (POCI-01–0145-FEDER-029250) and through Molecules for Health project (PTDC/ BIA-BQM/28355/2017). This work was also funded by the Integrated Programme of SR&TD Smart Valorization of Endogenous Marine Biological Resources Under a Changing Climate (Centro01–0145-FEDER-000018), co-funded by Centro 2020 Programme, Portugal 2020, European Union, through the European Regional Development Fund.
dc.description.abstractThe treatment of Parkinson´s disease (PD) has benefited from significant advances resulting from the increasing research efforts focused on new therapeutics. However, the current treatments for PD are mostly symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Thus, it is critical to find new molecules that can result in more effective treatments. Within this framework, this study aims to evaluate the neuroprotective and anti-inflammatory effects of three compounds (eleganolone, eleganonal and fucosterol) isolated from the brown seaweed Bifurcaria bifurcata. In vitro neuroprotective effects were evaluated on a PD cellular model induced by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, while lipopolysaccharide (LPS) -stimulated RAW 264.7 macrophages were used to evaluate the anti-inflammatory potential. Additionally, the underlying mechanisms of action were also investigated. Compounds were isolated by preparative chromatographic methods and their structural elucidation attained by NMR spectroscopy. Among the tested compounds, eleganolone (0.1–1 μM; 24 h) reverted the neurotoxicity induced by 6-OHDA in about 20%. The neuroprotective effects were mediated by mitochondrial protection, reduction of oxidative stress, inflammation and apoptosis, and inhibition of NF-kB pathway. The results suggest that eleganolone may provide advantages in the treatment of neurodegenerative conditions and, therefore, should be considered for future preclinical studies.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJoana Silva, Celso Alves, Susete Pinteus, Patrícia Susano, Marco Simões, Miguel Guedes, Alice Martins, Stephanie Rehfeldt, Helena Gaspar, Márcia Goettert, Amparo Alfonso, Rui Pedrosa, Disclosing the potential of eleganolone for Parkinson’s disease therapeutics: Neuroprotective and anti-inflammatory activities, Pharmacological Research, Volume 168, 2021, 105589, ISSN 1043-6618, https://doi.org/10.1016/j.phrs.2021.105589pt_PT
dc.identifier.doi10.1016/j.phrs.2021.105589pt_PT
dc.identifier.issn1043-6618
dc.identifier.urihttp://hdl.handle.net/10400.8/5996
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationMarine and Environmental Sciences Centre
dc.relationMarine and Environmental Sciences Centre
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1043661821001730?via%3Dihubpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectApoptosispt_PT
dc.subjectDiterpenespt_PT
dc.subjectMarine natural productspt_PT
dc.subjectNF-kB pathwaypt_PT
dc.subjectNeurodegenerative diseasespt_PT
dc.subjectOxidative stresspt_PT
dc.titleDisclosing the potential of eleganolone for Parkinson’s disease therapeutics: neuroprotective and anti-inflammatory activitiespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleMarine and Environmental Sciences Centre
oaire.awardTitleMarine and Environmental Sciences Centre
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBIA-OUT%2F29250%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIA-BQM%2F28355%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04292%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04292%2F2020/PT
oaire.citation.titlePharmacological Researchpt_PT
oaire.citation.volume168pt_PT
oaire.fundingStream9471 - RIDTI
oaire.fundingStream3599-PPCDT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
person.familyNameSilva
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person.familyNameFrederico Susano
person.familyNameDias Simões
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person.familyNameGuerreiro Galla Gaspar
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person.familyNameAlfonso Rancaño
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person.givenNameStephanie
person.givenNameHelena Margarida
person.givenNameMárcia Inês
person.givenNameMaria Amparo
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project.funder.identifierhttp://doi.org/10.13039/501100001871
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project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
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