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

The 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.

Descrição

FCT 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.

Palavras-chave

Apoptosis Diterpenes Marine natural products NF-kB pathway Neurodegenerative diseases Oxidative stress

URI

http://hdl.handle.net/10400.8/5996

Citação

Joana 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.2021.105589