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

Publication . Silva, Joana; Alves, Celso; Pinteus, Susete; Susano, Patrícia; Simões, Marco; Guedes, Miguel; Martins, Alice; Rehfeldt, Stephanie; Gaspar, Helena; Goettert, Márcia Inês; Alfonso, Amparo; Pedrosa, Rui

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.

2021Journal article

Restricted access

Loliolide, a new therapeutic option for neurological diseases? In vitro neuroprotective and anti-inflammatory activities of a monoterpenoid lactone isolated from codium tomentosum

Publication . Silva, Joana; Alves, Celso; Martins, Alice; Susano, Patrícia; Simões, Marco; Guedes, Miguel; Rehfeldt, Stephanie; Pinteus, Susete; Gaspar, Helena; Rodrigues, Américo; Goettert, Márcia Inês; Alfonso, Amparo; Pedrosa, Rui

Parkinsons Disease (PD) is the second most common neurodegenerative disease worldwide, and is characterized by a progressive degeneration of dopaminergic neurons. Without an effective treatment, it is crucial to find new therapeutic options to fight the neurodegenerative process, which may arise from marine resources. Accordingly, the goal of the present work was to evaluate the ability of the monoterpenoid lactone Loliolide, isolated from the green seaweed Codium tomentosum, to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells and their anti-inflammatory effects in RAW264.7 macrophages. Loliolide was obtained from the diethyl ether extract, purified through column chromatography and identified by NMR spectroscopy. The neuroprotective effects were evaluated by the MTT method. Cells’ exposure to 6-OHDA in the presence of Loliolide led to an increase of cells’ viability in 40%, and this effect was mediated by mitochondrial protection, reduction of oxidative stress condition and apoptosis, and inhibition of the NF-KB pathway. Additionally, Loliolide also suppressed nitric oxide production and inhibited the production of TNF- and IL-6 pro-inflammatory cytokines. The results suggest that Loliolide can inspire the development of new neuroprotective therapeutic agents and thus, more detailed studies should be considered to validate its pharmacological potential.

2021Journal article

Open access

Undaria pinnatifida (U. pinnatifida) bioactivity: Antioxidant, gastro-intestinal motility, cholesterol biosynthesis and liver cell lines proteome

Publication . Pedro, Bernardo; Guedes, Laura; André, Rebeca; Gaspar, Helena; Vaz, Pedro; Ascensão, Lia; Melo, Ricardo; Serralheiro, Maria Luisa

Undaria pinnatifida is a brown alga, largely used as food in oriental countries. The purpose of this work was to analyze several bioactivities that might be present in different food preparations, relating them with the compounds present in the extracts. Aqueous extracts cooked, like a soup, as well as used in a salad, by simulating U. pinnatifida digestion with pancreatin were prepared. The soup preparation had anti-acetylcholinesterase activity as well as 3-hydroxy3-methyl-glutaryl coenzyme A reductase inhibition capacity, the use of 1 mg/mL, for both enzymes, caused 50% enzyme activity inhibition. The extracts produced changes in HepG2 cell proteome, mainly in the 148 kDa proteins. U. pinnatifida in salads hardly released phlorotannins to the digestive tract. The in vitro studies suggested that a soup prepared from this seaweed could deliver bioactive compounds, phlorotannins and small peptides that may facilitate the gastro-intestinal motility and reduce the cholesterol biosynthesis.

2021Journal article

Open 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

Exploring marine resources against neurological disorders: the neuroprotective and anti‑inflammatory potential of the brown seaweed Bifurcaria bifurcata

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

Oxidative stress is strongly involved in the pathogenesis of neurodegenerative diseases, like Parkinson´s disease (PD). Particularly, an excess of reactive oxygen species (ROS) released by the cells promotes an oxidative stress condition, which is a main cause of tissue injury leading to nervous system dysfunction. In this work, the antioxidant, neuroprotective and antiinflammatory activities of different fractions from the brown seaweed Bifurcaria bifurcata are presented and related with their chemical profile. The antioxidant capacity was evaluated by the Folin-Ciocalteu method, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Neuroprotective capacity was evaluated to prevent neurological cell death mediated by the neurotoxin 6-hydroxydopamine (6-OHDA) on SH-SY5Y cells, and their anti-inflammatory effects on RAW 264.7 macrophages. The ethyl acetate fractions (100 μg mL−1) exhibited significant antioxidant and neuroprotective activities in the in vitro models assayed. Furthermore, two of the most polar fractions obtained with methanol and water also evidenced a significant neuroprotective potential. Bifurcaria bifurcata fractions treatment decreased ROS production, mitochondrial dysfunction, and Caspase-3 activity. Regarding the anti-inflammatory potential, five fractions (100 μg mL−1) inhibited nitric oxide (NO) production and reduced the interleukin – 6 (IL-6) and tumor necrosis factor (TNF-α) levels. Mannitol, identified as the major component of the most bioactive fraction, protected SH-SY5Y cells against the 6-OHDA neurotoxicity mediating ROS generation mitigation, mitochondrial dysfunction, and DNA damage, together with the Caspase-3 activity inhibition. Results suggest that B. bifurcata is a relevant source of neuroprotective agents, with particular interest for preventive therapeutics.

2022Journal article

Restricted access