Biologically Active Natural Products from Marine Organisms and Salt Marsh Plants (acronym: PharmaBlue)

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In vitro and in silico approaches to appraise Polygonum maritimum L. as a source of innovative products with anti-ageing potential

Publication . Rodrigues, Maria Joao; Slusarczyk, Sylwester; Pecio, Łukasz; Matkowski, Adam; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Pereira, Catarina; Varela, J.; Barreira, Luísa; Custódio, Luísa

Different Polygonum species have in vitro neuroprotective properties and are traditionally used for their anti-ageing benefits. In this context this work explored for the first time P. maritimum (sea knotgrass) as a potential source of natural products with industrial application as cognitive enhancers with anti-ageing potential. For that purpose methanol and dichloromethane extracts were prepared from leaves and roots of that species and evaluated for in vitro neuroprotective effects through the inhibition on acetyl- (AChE) and butyrylcholinesterase (BuChE), protection against hydrogen peroxide (H2O2)-induced cytoxicity on neuroblastoma cells and lipopolysaccharide (LPS)-induced neuroinflammation on microglia cells. The extracts were chemically characterized by ultra-high-pressure liquid chromatography (UHPLC) coupled to tandem mass spectrometry (MS/MS) and docking studies were performed on the identified compounds. Methanol extracts had the highest activity in AChE (leaves: IC50 = 0.27 mg/mL; roots: IC50 = 0.17 mg/mL) and BuChE (leaves: IC50 = 0.62 mg/mL; roots: IC50 = 0.61 mg/mL) inhibition, as well as reduction of nitric oxide (NO) production in LPS-treated microglia (leaves: IC50 = 4.17 μg/mL; roots: IC50 = 9.95 μg/mL). Methanol extracts prevented oxidative stress-induced cytotoxicity in SH-SY5Y cells when applied simultaneously with H2O2, whereas cells pre-treated with the dichloromethane extracts had increased viability. Fifteen flavonoids were identified and showed favorable binding energies to AChE and BuChE binding pockets. These data suggests P. maritimum as a promising source of natural products and/or molecules with cognitive enhancement and anti-ageing properties.

2018-01Journal article

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Natural products from marine invertebrates against Leishmania parasites: a comprehensive review

Publication . Oliveira, Marta; Barreira, Luísa; Gangadhar, Katkam N.; Rodrigues, Maria Joao; Santos, Tamara; Varela, J.; Custódio, Luísa

Parasitic infections by Leishmania parasites remains a severe public health problem, especially in developing countries where it is highly endemic. Chemotherapy still remains a first option for the treatment of those diseases, despite the fact that available drugs exhibit a variety of shortcomings. Thus, innovative, less toxic more affordable and effective antileishmanial agents are urgently needed. The marine environment holds an immeasurable bio- and chemical diversity, being a valuable source of natural products with therapeutic potential. As invertebrates comprise about 60 % of all marine organisms, bioprospecting this class of organisms for antileishmanial properties may unravel unique and selective hit molecules. In this context, this review covers results on the literature of marine invertebrate extracts and pure compounds evaluated against Leishmania parasites mainly by in vitro methods. It comprises results obtained from the phyla Porifera, Cnidaria, Bryozoa (Ectoprota), Mollusca, Echinodermata, Annelida, Cetnophora, Platyhelminthes, sub phyla Crustacea (phylum Arthropoda) and Tunicata (phylum Chordata). Moreover, structure-activity relationships and possible mechanisms of action are mentioned, whenever available information is provided. About 70 species of marine invertebrates belonging to seven different phyla are included in this work. Besides a variety of crude extracts, a total of 140 pure compounds was tested against different Leishmania species. Although the research on the antileishmanial potential of marine invertebrates is in its early beginnings, promising results have been achieved that encourage further research. As more extracts and compounds are being screened, the possibility of finding active and selective antileishmanial molecules increases, rising new hope in the search for new treatments against leishmaniases.

2016-08Journal article

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Natural products from extreme marine environments: searching for potential industrial uses within extremophile plants

Publication . Lopes, Andreia; Rodrigues, Maria João; Pereira, Catarina; Oliveira, Marta; Barreira, Luísa; Varela, J.; Trampetti, Francesca; Custódio, Luísa

Extremophile plants, halophytes in particular, still remain largely unexplored and underutilized despite their high potential as source of industrial raw materials like natural antioxidants in industries related to pharmaceutical, cosmetics and functional ingredients. The goal of this study was to explore the phenolic content and the in vitro antioxidant and tyrosine inhibition properties of polyphenol-rich extracts of twenty-one extremophile plant species collected in saline habitats of the South of Portugal (Algarve). Aqueous acetone extracts of Lithrum salicaria, Cladium mariscus, Frankenia laevis, F. pulverulenta, Limoniastrum monopetalum, Aster tripolium and Typha domigensis had remarkable levels of total phenolics (>= 230 mg GAE/g DW); Halopeplis amplexicaulis, Cladium mariscus,F. puiverulenta and Salsola vermiculata contained high levels of flavonoids (>= 10 mg RE/g DW); tannins peaked in T. domingensis and C. mariscus (>= 35 mg CE/g DW) and L. salicaria and A. tripolium had the upmost hydrocinamic acids content (>= 60 mg CAE/g DW). Overall L. salicaria had the highest antioxidant activity and only P. lentiscus had the capacity to inhibit tyrosinase. As the most bioactive extracts were not cytotoxic towards mammalian cell lines, our results suggest that several halophytes present in Southern Portugal could be used in the food and/or cosmetic industries.

2016-12Journal article

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Profiling of antioxidant potential and phytoconstituents of Plantago coronopus

Publication . Pereira, C. G.; Custódio, Luísa; Rodrigues, Maria João; Neng, N. R.; Nogueira, J. M. F.; Carlier, Jorge; Costa, Maria Clara; Varela, J.; Barreira, Luísa

The halophyte species Plantago coronopus has several described ethnomedicinal uses, but few reported biological activities. This work carried out for the first time a comparative analysis of P. coronopus organs in terms of phenolic composition and antioxidant activity of organic and water extracts from roots, leaves and flowers. The leaves contents in selected nutrients, namely amino acids and minerals, are also described. Roots (ethyl acetate and methanol extracts) had the highest radical scavenging activity (RSA) towards 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals, while leaves (hexane extract) had higher RSA on nitric oxide radical and iron chelating ability. High performance liquid chromatography (HPLC) analysis identified eighteen phenolics from which salicylic acid and epicatechin are here firstly described in Plantago species. Leaves had mineral levels similar to those of most vegetables, proving to be a good source for elements like calcium, sodium, iron and magnesium, and also for several of the essential amino acids justifying it use as food. Our results, especially those regarding the phenolics composition, can explain the main traditional uses given to this plantain and, altogether, emphasize the potential of P. coronopus as a source of bioactive molecules particularly useful for the prevention of oxidative stress-related diseases.

2016-11Journal article

Open Access

Seagrass debris as potential food source to enhance Holothuria arguinensis' growth in aquaculture

Publication . Dominguez Godino, Jorge Antonio; Santos, Tamara; H., Pereira; Custódio, Luísa; Gonzalez-Wanguemert, Mercedes

Holothuria arguinensis aquaculture started to be developed in 2014, being the first sea cucumber species from Europe. However, some aspects of its aquaculture biotechnology, such diets, need to be assessed. This work aimed to evaluate seagrass debris of Zostera noltii and Cymodocea nodosa as food source for broodstock maintenance in tanks, during breeding periods. The given feed rations per tank were calculated as the 30% of the total sea cucumber biomass in each tank and reviewed each week. Then, feed rations of seagrass and sediment were calculated from this value, according to the following percentages: 40% sediment, 15% Z. noltii, 40% Z. noltii, 15% C. nodosa and 40% C. nodosa. H. arguinensis growth, feeding rate and nutritional value were assessed under these diets. H. arguinensis fed with 40% of Z. noltii showed the highest growth (specific growth rate = 0.09 +/- 0.06%/day, absolute growth rate = 0.11 +/- 0.07 g/day) increasing their final weight in 5.86 +/- 3.57% in 57 days. However, the individuals fed with C. nodosa showed a negative growth. H. arguinensis showed a reduction in its feeding rate as the organic matter content in the diets increased. H. arguinensis did not show any important change on proximate composition, protein, lipid, mineral contents and fatty acids profile among the feeding groups, or in comparison with the individuals collected from wild habitat. Therefore, H. arguinensis could be fed with Z. noltii debris during tanks maintenance along breeding period, ensuring its growth and maintaining its nutritional profile.

2020-04Journal article

Open Access