Neuroprotective effects of molecules isolated from Bifurcaria bifurcata and Codium tomentosum in an in vitro and in vivo Parkinson Disease model.

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Seaweeds’ neuroprotective potential set in vitro on a human cellular stress model

Publication . Silva, Joana; Alves, Celso; Pinteus, Susete; Mendes, Susana; Pedrosa, Rui

Neurodegenerative diseases, such as Parkinson’s disease, represent a biggest challenge for medicine, imposing high social and economic impacts. As a result, it is of utmost importance to develop new therapeutic strategies. The present work evaluated the neuroprotective potential of seaweeds extracts on an in vitro dopamine (DA)-induced neurotoxicity cellular model. The neuroprotective effects on SH-SY5Y cells’ viability were estimated by the MTT assay. Changes in mitochondrial membrane potential (MMP), caspase-3 activity, and hydrogen peroxide (H2O2) production were determined. DA (30–3000 μM; 24 h) treatment decreased SH-SY5Y cells’ viability in concentration and time-dependent manner, increasing the H2O2 production, MMP depolarization, and caspase-3 activity. On the other hand, DA (1000 μM; 24 h) toxicity was reduced (10–15%) with Sargassum muticum and Codium tomentosum extracts (1000 μg/mL; 24 h). The highest neuroprotective activity was exhibited by a methanolic extract obtained from Saccorhiza polyschides, which completely blunted DA effects. Results show that the marine seaweed S. polyschides contain substances with high neuroprotective potential against the toxicity induced by DA, exhibiting anti-apoptotic effects associated with both mitochondrial protection and caspase-3 inhibition. S. polyschides reveals, therefore, to be an excellent source of bioactive molecules, for new drugs development aiming PD therapeutics.

2020Journal article

Restricted access

Marine invasive macroalgae: Turning a real threat into a major opportunity - the biotechnological potential of Sargassum muticum and Asparagopsis armata

Publication . Pinteus, Susete; Lemos, Marco F.L.; Alves, Celso; Neugebauer, Agnieszka; Silva, Joana; Thomas, Olivier P.; Botana, Luis M.; Gaspar, Helena; Pedrosa, Rui

Marine invasive species are widely recognized as one of the worst threats to marine ecosystems integrity, un-balancing native communities, which may lead to paramount ecological and economic impacts. Within invasiveseaweeds, Sargassum muticum and Asparagopsis armata are recognized as successful invaders in Europe andAmerica. Despite several attempts to control the spread of marine invaders, until now, all have proven to beelusive, and therefore, alternative strategies should be embraced.Worldwide, seaweeds have been increasingly explored due to their ability to produce bioactive compounds.However, one of the main problems associated with the production/extraction of these bioactive compounds fornew products development, is the source availability and the potential negative environmental consequences ofthis exploitation.Within this framework, the use of invasive species to obtain natural bioactive compounds presents us with atwo-folded opportunity - high availability of the biological material for the extraction of unique bioactivecompounds for new products development, and through specimen collection, mitigating negative eﬀects causedby alien species, contributing for ecosystem integrity and sustainability.Over the last decades, the brown seaweed S. muticum and the red A. armata have been studied all over theworld for their capacity to produce bioactive compounds, with main results pointing towards their high potentialas producers of antioxidant, antifouling, antimicrobial, and antitumor compounds.The present review summarizes the biotechnological potential of S. muticum and A. armata as producers ofbioactive compounds, while addressing the potential use of global threats as important blue growth pawns.

2018-08-08Journal article

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Sphaerococcus coronopifolius bromoterpenes as potential cancer stem cell-targeting agents

Publication . Alves, Celso; Serrano, Eurico; Silva, Joana; Rodrigues, Carlos; Pinteus, Susete; Gaspar, Helena; Botana, Luis M.; Alpoim, Maria C.; Pedrosa, Rui

Cancer is one of the major threats to human health and, due to distinct factors, it is expected that its incidence will increase in the next decades leading to an urgent need of new anticancer drugs development. Ongoing experimental and clinical observations propose that cancer cells with stem-like properties (CSCs) are involved on the development of lung cancer chemoresistance. As tumour growth and metastasis can be controlled by tumourassociated stromal cells, the main goal of this study was to access the antitumor potential of five bromoterpenes isolated from Sphaerococcus coronopifolius red alga to target CSCs originated in a co-culture system of fibroblast and lung malignant cells. Cytotoxicity of compounds (10–500 μM; 72 h) was evaluated on monocultures of several malignant and non-malignant cells lines (HBF, BEAS-2B, RenG2, SC-DRenG2) and the effects estimated by MTT assay. Co-cultures of non-malignant human bronchial fibroblasts (HBF) and malignant human bronchial epithelial cells (RenG2) were implemented and the compounds ability to selectively kill CSCs was evaluated by sphere forming assay. The interleucine-6 (IL-6) levels were also determined as cytokine is crucial for CSCs. Regarding the monocultures results bromosphaerol selectively eliminated the malignant cells. Both 12S-hydroxy-bromosphaerol and 12R-hydroxy-bromosphaerol steroisomers were cytotoxic towards non-malignant bronchial BEAS-2B cell line, IC50 of 4.29 and 4.30 μM respectively. However, none of the steroisomers induced damage in the HBFs. As to the co-cultures, 12R-hydroxy-bromosphaerol revealed the highest cytotoxicity and ability to abrogate the malignant stem cells; however its effects were IL-6 independent. The results presented here are the first evidence of the potential of these bromoterpenes to abrogate CSCs opening new research opportunities. The 12R-hydroxy-bromosphaerol revealed to be the most promising compound to be test in more complex living models.

2020Journal article

Restricted access

Natural approaches for neurological disorders: The neuroprotective potential of Codium tomentosum

Publication . Silva, Joana; Martins, Alice; Alves, Celso; Pinteus, Susete; Gaspar, Helena; Alfonso, Amparo; Pedrosa, Rui

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and is characterized by a progressive degeneration of the dopaminergic neurons in the substantia nigra. Although not completely understood, several abnormal cellular events are known to be related with PD progression, such as oxidative stress, mitochondrial dysfunction and apoptosis. Accordingly, the aim of this study was to evaluate the neuroprotective e ects of Codium tomentosum enriched fractions in a neurotoxicity model mediated by 6-hydroxydopamine (6-OHDA) on SH-SY5Y human cells, and the disclosure of their mechanisms of action. Additionally, a preliminary chemical screening of the most promising bioactive fractions of C. tomentosum was carried out by GC-MS analysis. Among the tested fractions, four samples exhibited the capacity to revert the neurotoxicity induced by 6-OHDA to values higher or similar to the vitamin E (90.11 +- 3.74% of viable cells). The neuroprotective e ects were mediated by the mitigation of reactive oxygen species (ROS) generation, mitochondrial dysfunctions and DNA damage, together with the reduction of Caspase-3 activity. Compounds belonging to different chemical classes, such as terpenes, alcohols, carboxylic acids, aldehydes, esters, ketones, saturated and unsaturated hydrocarbons were tentatively identified by GC-MS. The results show that C. tomentosum is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.

2020Journal article

Open access

An Insight into Sargassum muticum Cytoprotective Mechanisms against Oxidative Stress on a Human Cell In Vitro Model

Publication . Pinteus, Susete; Lemos, Marco; Silva, Joana; Alves, Celso; Neugebauer, Agnieszka; Freitas, Rafaela; Duarte, Adriana; Pedrosa, Rui

Sargassum muticum is a brown seaweed with strong potential to be used as a functional food ingredient, mainly due to its antioxidant properties. It is widely used in traditional oriental medicine for the treatment of numerous diseases. Nevertheless, few studies have been conducted to add scientific evidence on its effects as well as on the mechanisms of action involved. In this work, the human cell line MCF-7 was used as an in vitro cellular model to evaluate the capability of Sargassum muticum enriched fractions to protect cells on an oxidative stress condition. The concentration of the bioactive compounds was obtained by vacuum liquid chromatography applied on methanol (M) and 1:1 methanol:dichloromethane (MD) crude extracts, resulting in seven enriched fractions from the M extraction (MF2-MF8), and eight fractions from the MD extraction (MDF1-MDF8). All fractions were tested for cytotoxic properties on MCF-7 cells and the nontoxic ones were tested for their capacity to blunt the damaging effects of hydrogen peroxide-induced oxidative stress. The nontoxic effects were also confirmed in 3T3 fibroblast cells as a nontumor cell line. The antioxidant potential of each fraction, as well as changes in the cell's real-time hydrogen peroxide production, in the mitochondrial membrane potential, and in Caspase-9 activity were evaluated. The results suggest that the protective effects evidenced by S. muticum can be related with the inhibition of hydrogen peroxide production and the inhibition of Caspase-9 activity.

2017Journal article

Open access