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Neuroprotective activity of Eleganolone diterpene isolated from seaweed Bifurcaria bifurcata on an in vitro model of Parkinson disease

Joana Silva1, 2, Celso Alves1, Rafaela Freitas Freitas1, Susete G. Pinteus1, Joana Margarida D. Ribeiro1, Helena Gaspar1, 3 and Rui P. Pedrosa1*
  • 1 MARE – Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria, Portugal
  • 2 Facultad de Veterinaria, Universidad de Santiago de Compostela, Department of Pharmacology, Spain
  • 3 Instituto de Biossistemas e Ciências Integrativas (BioISI), Portugal

Oxidative stress, mitochondrial dysfunction and apoptosis seem to be involved in the pathogenesis of Parkinson Disease which is characterized by the loss of dopaminergic cell bodies in the substantia nigra and depletion of neurotransmitter dopamine (DA) [1]. Eleganolone is a diterpene previously isolated from the brown seaweed Bifurcaria bifurcatathat revealed cytotoxic and antiprotozal activities [2,3]. However, its neuroprotective activity has never been studied. Therefore, the main aim of this study was to evaluate the neuroprotective activity of Eleganolone diterpene on 6-hydroxy-dopamine (6-OHDA)-induced neurotoxicity in the human neuroblastoma cell line SH-SY5Y, as well as the associated intracellular signaling pathways. SH-SY5Y cells were pre-incubated 1 hour with different concentrations of Eleganolone (0.05 - 5µM). Following, 6 – OHDA (100 µM) was added and cells incubated 24 hours. The effects were revealed by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) method. The neuroprotective effects of Eleganolone on mitochondrial membrane potential, H2O2 production and Caspase-3 activity were verified in the presence of 6 – OHDA. Eleganolone demonstrated capacity to recover the neurotoxicity induced by 6-OHDA in 18.28% and 25.53% at the concentrations of 0.5 and 1 µM, respectively. The neuroprotective activity of this compound was mediated by the protection of mitochondrial function (23.3% and 23.6% at 0.5 and 1 µM, respectively), a decrease of Caspase-3 activity (76% and 75% at 0.5 and 1 µM, respectively) and a decrease of H2O2 production (41.5% at 0.5 µM), when compared with 6-OHDA treatment. In conclusion, the Eleganolone diterpene reveals neuroprotective activity, showing potential to be used for the development of new therapeutic approaches for Parkinson disease.

Acknowledgements

Authors would like to acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) through Strategic Project UID/MAR/04292/2013 granted to MARE – Marine and Environmental Sciences Centre and through Oncologia de Precisão: Terapias e Tecnologias Inovadoras project (POINT4PAC) (SAICTPAC/0019/2015 - LISBOA-01-0145-FEDER-016405). Joana Silva is financial supported by a grant from FCT (SFRH/BD/103255/ 2014).

References

1. Ramkumar, M. et al. Neuroprotective effect of Demethoxycurcumin, a natural derivative of Curcumin on rotenone induced neurotoxicity in SH-SY 5Y Neuroblastoma cells. BMC Complementary and Alternative Medicine 17, 1–11 (2017).
2. Gallé, J. B. et al. Eleganolone, a Diterpene from the French marine alga bifurcaria bifurcata inhibits growth of the human pathogens trypanosoma brucei and plasmodium falciparum. Marine Drugs 11, 599–610 (2013).
3. Göthel, Q., Lichte, E. & Köck, M. Further eleganolone-derived diterpenes from the brown alga Bifurcaria bifurcata. Tetrahedron Letters 53, 1873–1877 (2012).

Keywords: Natural Products, SH-SY5Y cell line, Apoptose, Oxidative Stress, Bioative compounds

Conference: IMMR'18 | International Meeting on Marine Research 2018, Peniche, Portugal, 5 Jul - 6 Jul, 2018.

Presentation Type: Poster Presentation

Topic: Blue Biotech

Citation: Silva J, Alves C, Freitas R, Pinteus SG, Ribeiro JD, Gaspar H and Pedrosa RP (2019). Neuroprotective activity of Eleganolone diterpene isolated from seaweed Bifurcaria bifurcata on an in vitro model of Parkinson disease. Front. Mar. Sci. Conference Abstract: IMMR'18 | International Meeting on Marine Research 2018. doi: 10.3389/conf.fmars.2018.06.00163

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Received: 27 Jul 2018; Published Online: 07 Jan 2019.

* Correspondence: PhD. Rui P Pedrosa, MARE – Marine and Environmental Sciences Centre, ESTM, Polytechnic Institute of Leiria, Peniche, Portugal, rpedrosa@ipleiria.pt