Bioactive Marine Drugs and Marine Biomaterials for Brain Diseases

Marine invertebrates produce a plethora of bioactive compounds, which serve as inspiration for marine biotechnology, particularly in drug discovery programs and biomaterials development. This review aims to summarize the potential of drugs derived from marine invertebrates in the field of neuroscience. Therefore, some examples of neuroprotective drugs and neurotoxins will be discussed. Their role in neuroscience research and development of new therapies targeting the central nervous system will be addressed, with particular focus on neuroinflammation and neurodegeneration. In addition, the neuronal growth promoted by marine drugs, as well as the recent advances in neural tissue engineering, will be highlighted.The authors are grateful to the financial support from the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013 and from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07–0124-FEDER-000069, to CYTED Programme (Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011–23690 (CICYT). Clara Grosso thanks FCT for the Post-Doc fellowship (SFRH/BPD/63922/2009). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)Peer reviewe

Alternative and efficient extraction methods for marine-derived compounds

Marine ecosystems cover more than 70% of the globe's surface. These habitats are occupied by a great diversity of marine organisms that produce highly structural diverse metabolites as a defense mechanism. In the last decades, these metabolites have been extracted and isolated in order to test them in different bioassays and assess their potential to fight human diseases. Since traditional extraction techniques are both solvent- and time-consuming, this review emphasizes alternative extraction techniques, such as supercritical fluid extraction, pressurized solvent extraction, microwave-assisted extraction, ultrasound-assisted extraction, pulsed electric field-assisted extraction, enzyme-assisted extraction, and extraction with switchable solvents and ionic liquids, applied in the search for marine compounds. Only studies published in the 21st century are considered. © 2015 by the authors; licensee MDPI.The authors are grateful for the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundação para a Ciência e Tecnologia) through project Pest-C/EQB/LA0006/2013, to financial support from the European Union (FEDER funds) under the framework of QREN through Project NORTE-07-0124-FEDER-000069, to CYTED Programme (Ref. 112RT0460) CORNUCOPIA Thematic Network and project AGL2011-23690 (CICYT). Clara Grosso thanks FCT for the FCT Investigator (IF/01332/2014). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

HPLC–DAD of phenolics in bryophytes Lunularia cruciata, Brachytheciastrum velutinum and Kindbergia praelonga

The chemistry of bryophytes is not well known. The available data indicate interesting chemical constitutions of some bryophyte species, i.e., active and new compounds are to be found within bryophytes, especially liverworts. In this study, one liverwort and two moss species were studied: Lunularia cruciata (L.) Dumort, Brachytheciastrum velutinum (Hedw) Ignatov & Huttunen and Kindbergia praelonga (Hedw) Ochyra. The phenolic compositions of these bryophyte species have not hitherto been reported. Their methanolic extracts were analyzed by reversed-phase HPLC, coupled to a diode-array detector (DAD). Luteolin-7-O-glucoside and quercetin were found in the L. cruciata extract. The extract obtained from B. velutinum contained four phenolic acids (4-O-caffeoylquinic, 5-O-caffeoylquinic, caffeic and ellagic acids) and three flavonoids (apigenin-7-O-glucoside, luteolin and apigenin). The K. praelonga extract was characterized by the presence of several phenolic acids and their derivatives (4-O-caffeoylquinic, 5-O-caffeoylquinic, caffeic, p-coumaric, ferulic and ellagic acids, and caffeic and p-coumaric acid derivatives) and three flavonoids (apigenin-7-O-glucoside, luteolin, apigenin and an un-identified flavanone)

Do bioactive carotenoids contribute to the color of edible mushrooms?

Carotenoids are biologically active phytochemicals present as micro-components in fruits and vegetables, being responsible for their yellow, orange and red colors. The chromatographic behavior and the UV absorption spectrum provided by HPLC-DAD analysis constitute the clues for their identification. Mushrooms are of increasing importance in modern nutrition and medicine, due to the presence of metabolites with pharmacological potential. In this work, samples of wild and commercial mushroom species (Agaricus bisporus, Amanita caesarea, Amanita rubescens, Boletus edulis, Cantharellus cibarius, Fistulina hepatica, Hydnum rufescens, Hygrophorus agathosmus, Pholiota nameko, Pleurotus ostreatus, Russula cyanoxantha, Suillus bellini, Suillus bovinus, Suillus granulatus, Suillus luteus, Tricholoma equestre and Tricholoma portentosum) were screened by HPLC-DAD for the presence of carotenoids. By applying this methodology to 22 samples, comprising either lyophilized or fresh materials, only β-carotene was found and just in C. cibarius species. The occurrence of this pigment in other three of the analyzed species previously described raises some questions about the methodology used.info:eu-repo/semantics/publishedVersio

Chemical ecology of echinoderms: Impact of environment and diet in metabolomic profile

The phylum Echinodermata constitutes a successful and widespread group comprising Asteroidea, Ophiuroidea, Echinoidea, Holothuroidea and Crinodeia. Nowadays, marine organisms are being given a lot of attention in drug discovery pipelines. In these studies, sponges and nudibranchs are frequently addressed, however an increasing number of works focus their attention in echinoderms. Given the fact that many of the bioactive molecules found in echinoderms are diet-derived, different feeding behavior and surrounding environment plays a critical role in the chemical composition of echinoderms. In this work, the most relevant chemical classes of small molecules present in echinoderms, such as fatty acids, carotenoids and sterols will be addressed. When data is available, the influence of the environment on the chemical profile of these organisms will be discussed.(undefined

Toxicity and structure-activity relationship (SAR) of α, β-dehydroamino acids against human cancer cell lines

A library of N-protected dehydroamino acids, namely dehydroalanine, dehydroaminobutyric acid and dehydrophenylalanine derivatives, was screened in three human cancer cell lines [(lung (A549), gastric (AGS) and neuroblastoma (SH-SY5Y)] in order to characterize their toxicological profile and identify new molecules with potential anticancer activity. Results showed N-protected dehydrophenylalanine and dehydroaminobutyric acid derivatives have no or low toxicity for all tested cell lines. The N-protected dehydroalanines exhibit significant toxic effects and the AGS and SH-SY5Y cells were significantly more vulnerable than A549 cells. Four α,β- dehydroalanine derivatives, with IC50 < 62.5 μM, were selected to investigate the pathways by which these compounds promote cell death. All compounds, at their IC50 concentrations, were able to induce apoptosis in both AGS and SH-SY5Y cell lines. In both cell lines, loss of mitochondrial membrane potential (ΔΨm) was found and caspase activity was increased, namely endoplasmic reticulum-resident caspase-4 in AGS cells and caspase-3/7 in SH-SY5Y cells. When evaluated in a non-cancer cell line, the molecules displayed no to low toxicity, thus suggesting some degree of selectivity for cancer cells. The results indicate that α,β-dehydroalanine derivatives can be considered a future resource of compounds able to work as anticancer drugs.This work received financial support from National Funds (FCT/MEC) through Project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020); and from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-01-0145-FEDER 000024).info:eu-repo/semantics/publishedVersio

Synthesis and preliminary biological evaluation of new phenolic and catecholic dehydroamino acid derivatives

A library of N-phenolic and N-catecholic dehydroamino acid derivatives was prepared using an innovative synthetic strategy that involves mild reaction conditions and simple work-up procedures. The method comprises coupling of phenolic or catecholic acids with β-hydroxyamino acids followed by tert-butyloxycarbonylation of all hydroxyl groups using tert-butyldicarbonate and 4-dimethylaminopyridine as catalyst. Treatment of these amino acids with N,N,N’,N’-tetramethylguanidine affords the corresponding O-tert-butyloxycarbonyldehydro-amino acid derivative. Deprotection of the aromatic hydroxyl groups is carried out with trifluoroacetic acid. This synthetic strategy can be applied in a one-pot procedure and yields compounds that can be easily inserted into peptides or other biomolecules after cleavage of the C-protecting group. Preliminary studies of cell viability show that these new compounds display very low or no toxicity. These dehydroamino acids with a phenolic or catecholic moiety can have intrinsic biological activity or used to prepare new hydrogels that mimic mussel adhesive proteins.This work received financial support from the Foundation for Science and Technology (FCT, Portugal), through projects UID/QUI/00686/2013, UID/QUI/00686/2016 (CQUM) and UID/QUI/50006/2013-POCI-01-0145-FEDER-007265, co-financed by European Union (FEDER under the Partnership Agreement PT2020), and from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-010145-FEDER-24).info:eu-repo/semantics/publishedVersio

Xanthone biosynthesis and accumulation in calli and suspended cells of Hypericum androsaemum

Calli and suspended cells of Hypericum androsaemum accumulated high levels of 1,3,5,6 and 1,3,6,7 oxygenated xanthones. The major compounds include simple oxygenated xanthones or derivatives with prenyl, pyran or methoxyl groups, four of them being new natural compounds. A hypothetical biosynthetic scheme is proposed based on the isolated compounds and statistical analysis. Xanthone accumulation was influenced greatly by medium factors, namely hormone supplementation. Calli grown with 4.5 mM a-naphtaleneacetic acid (NAA) 2.3 mM kinetin (KIN) had the highest specific xanthone production (1.3% biomass dry weight (DW)), whereas suspended cells grown in similar medium accumulated a lower amount (0.87% DW). Calli displayed a negative linear relationship between total xanthone accumulation and NAA concentration, in the range of 4.5–22.5 mM. However, in this range the xanthone 1,3,6,7:1,3,5,6 ratio and the biomass production showed a positive linear relationship with NAA concentration. Substitution of 4.5 mM of NAA by the same molar amount of 2,4-dichlorophenoxyacetic acid (2,4-D), in the presence of 2.3 mM of KIN, caused a decrease in xanthone accumulation in calli. The use of N6-benzyladenine (BA) instead of KIN reduced xanthone production, independently of the auxin used. This effect was attenuated when both hormones were present.Fundação para a Ciência e a Tecnologia (FCT

The drinking of a Salvia officinalis infusion improves liver antioxidant status in mice and rats

In this study we evaluate the biosafety and bioactivity (antioxidant potential) of a traditional water infusion (tea) of common sage (Salvia officinalis L.) in vivo in mice and rats by quantification of plasma transaminase activities and liver GST and GR enzyme activities. The replacement of water by sage tea for 14 days in the diet of rodents did not affect the body weight and food consumption and did not induce liver toxicity. On the other hand, a significant increase of liver GST activity was observed in rats (24%) and mice (10%) of sage drinking groups. The antioxidant potential of sage tea drinking was also studied in vitro in a model using rat hepatocytes in primary culture. The replacement of drinking water with sage tea in the rats used as hepatocyte donors resulted in an improvement of the antioxidant status of rat hepatocytes in primary culture, namely a significant increase in GSH content and GST activity after 4 hours of culture. When these hepatocyte cultures were exposed to 0.75 or 1 mM of tert-butyl hydroperoxide for 1 hour, some protection against lipid peroxidation and GSH depletion was conferred by sage tea drinking. However, the cell death induced by t-BHP as shown by LDH leakage was not different from that observed in cultures from control animals. This study indicates that the compounds present in this sage preparation contain interesting bioactivities which improve the liver antioxidant potential.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/6942/2001, Programa Operacional “Ciência, Tecnologia, Inovação” (POCTI) - POCTI/AGR/43482/2001