Marine invertebrates have been attracting the attention of researchers for their application in nutrition, agriculture, and the pharmaceutical industry, among others. Concerning sea anemones (Cnidaria), little is known regarding their metabolic profiles and potential value as a source of pharmacologically-active agents. In this work, the chemical profiles of two species of sea anemones Actinia equina and Anemonia sulcata, were studied by high-performance liquid chromatography with diode-array detection (HPLC-DAD) and its impact upon immune and gastric cells was evaluated. In both species, the methylpyridinium alkaloid homarine was the major compound in aqueous extracts. The extracts were effective in reducing lipopolysaccharide (LPS)-induced levels of nitric oxide (NO) and intracellular reactive oxygen species (ROS) in a macrophage model of inflammation. Both the extracts and the alkaloid homarine were effective in inhibiting phospholipase A₂ (PLA₂), a pivotal enzyme in the initial steps of the inflammatory cascade. In order to mimic the oral consumption of these extracts; their effect upon human gastric cells was evaluated. While no caspase-9 activation was detected, the fact that the endoplasmic reticulum-resident caspase-4, and also caspase-3, were activated points to a non-classical mechanism of apoptosis in human gastric cells. This work provides new insights on the toxicity and biological potential of sea anemones increasingly present in human nutrition. Full article

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycaemia, and predicted by the World Health Organization as the expected 7th leading cause of death in 2030. Diabetes mellitus type 2 (DMT2) comprises the majority of diabetic individuals around the world (90%–95%). Pathophysiologically, this disorder results from a deregulation of glucose homeostasis, worsened by overweight and by a sedentary lifestyle, culminating in life-threatening cardiovascular events. The currently available anti-diabetic drugs are not devoid of undesirable side effects, sometimes responsible for poor therapeutic compliance. This represents a challenge for contemporary medicine, and stimulates research focused on the development of safer and more efficient anti-diabetic therapies. Amongst the most promising sources of new bioactive molecules, seaweeds represent valuable, but still underexploited, biofactories for drug discovery and product development. In this review, the role of phlorotannins, a class of polyphenols exclusively produced by brown seaweeds, in the management of DMT2 will be discussed, focusing on various pharmacologically relevant mechanisms and targets, including pancreatic, hepatic and intestinal enzymes, glucose transport and metabolism, glucose-induced toxicity and β-cell cytoprotection, and considering numerous in vitro and in vivo surveys. Full article

The marine environment is an important source of structurally-diverse and biologically-active secondary metabolites. During the last two decades, thousands of compounds were discovered in marine organisms, several of them having inspired the development of new classes of therapeutic agents. Marine mollusks constitute a successful phyla in the discovery of new marine natural products (MNPs). Over a 50-year period from 1963, 116 genera of mollusks contributed innumerous compounds, Aplysia being the most studied genus by MNP chemists. This genus includes 36 valid species and should be distinguished from all mollusks as it yielded numerous new natural products. Aplysia sea hares are herbivorous mollusks, which have been proven to be a rich source of secondary metabolites, mostly of dietary origin. The majority of secondary metabolites isolated from sea hares of the genus Aplysia are halogenated terpenes; however, these animals are also a source of compounds from other chemical classes, such as macrolides, sterols and alkaloids, often exhibiting cytotoxic, antibacterial, antifungal, antiviral and/or antifeedant activities. This review focuses on the diverse structural classes of secondary metabolites found in Aplysia spp., including several compounds with pronounced biological properties. Full article

Marine algae are rich and heterogeneous sources of great chemical diversity, among which oxylipins are a well-recognized class of natural products. Algal oxylipins comprise an assortment of oxygenated, halogenated, and unsaturated functional groups and also several carbocycles, varying in ring size and position in lipid chain. Besides the discovery of structurally diverse oxylipins in macroalgae, research has recently deciphered the role of some of these metabolites in the defense and innate immunity of photosynthetic marine organisms. This review is an attempt to comprehensively cover the available literature on the chemistry, biosynthesis, ecology, and potential bioactivity of oxylipins from marine macroalgae. For a better understanding, enzymatic and nonenzymatic routes were separated; however, both processes often occur concomitantly and may influence each other, even producing structurally related molecules. Full article

Microalgae are well known for their biotechnological potential, namely with regard to bioactive lipidic components—especially carotenoids and polyunsaturated fatty acids (PUFA), well-known for therapeutic applications based on their antioxidant capacity. The aim of this work was to evaluate the influence of four distinct food-grade solvents upon extractability of specific lipidic components, and on the antioxidant capacity exhibited against both synthetic (2,2-diphenyl-1-picrylhydrazyl (DPPH^•) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS^+•)) and biological reactive species (O₂^•- and ^•NO^-). A eukaryotic microalga (Scenedesmus obliquus (M2-1)) and a prokaryotic one (Gloeothece sp.) were used as case studies. Concerning total antioxidant capacity, the hexane:isopropanol (3:2) and acetone extracts of Sc. obliquus (M2-1) were the most effective against DPPH^• and ABTS^+•, respectively. Gloeothece sp. ethanol extracts were the most interesting scavengers of O₂^•-, probably due the high content of linolenic acid. On the other hand, acetone and hexane:isopropanol (3:2) extracts were the most interesting ones in ^•NO^- assay. Acetone extract exhibited the best results for the ABTS assay, likely associated to its content of carotenoids, in both microalgae. Otherwise, ethanol stood out in PUFA extraction. Therefore, profiles of lipidic components extracted are critical for evaluating the antioxidant performance—which appears to hinge, in particular, on the balance between carotenoids and PUFAs. Full article

The exploitation of marine organisms for human nutritional and pharmaceutical purposes has revealed important chemical prototypes for the discovery of new drugs, stimulating compounds isolation and syntheses of new related compounds with biomedical application. Nowadays, it is well known that inflammatory processes are involved in many diseases and the interest in the search for marine natural products with anti-inflammatory potential has been increasing. The genus Aplysia belongs to the class Gastropoda, having a wide geographical distribution and including several species, commonly known as sea hares. Aplysia depilans Gmelin is usually found in the Mediterranean Sea and in the Atlantic Ocean, from West Africa to the French coast. In these marine organisms, most of the digestion and nutrient absorption occurs in the digestive gland. This work aimed to explore the chemical composition and bioactivity of the methanol extract from A. depilans digestive gland. Therefore, fatty acids and carotenoids were determined by GC-MS and HPLC-DAD, respectively. Twenty-two fatty acids and eight carotenoids were identified for the first time in this species. The A. depilans digestive gland revealed to be essentially composed by polyunsaturated fatty acids (PUFA) and xanthophylls. Regarding the anti-inflammatory potential in RAW 264.7 cells stimulated with lipopolysaccharide, it was observed that this matrix has capacity to reduce nitric oxide (NO) and L-citrulline levels, which suggests that its compounds may act by interference with inducible nitric oxide synthase. Taking into account the results obtained, A. depilans digestive gland may be a good source of nutraceuticals, due to their richness in health beneficial nutrients, such as carotenoids and long-chain PUFA. Full article

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer’s disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O₂˙⁻) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC₅₀ values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities. Full article

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. Full article

There is an increasing body of evidence of the positive impact of several marine lipids on human health. These compounds, which include ω-3 polyunsaturated fatty acids, have been shown to improve blood lipid profiles and exert anti-inflammatory and cardioprotective effects. The high instability of these compounds to oxidative deterioration and their hydrophobicity have a drastic impact in their pharmacokinetics. Thus, the bioavailability of these compounds may be affected, resulting in their inability to reach the target sites at effective concentrations. In this regard, micro/nanoparticles can offer a wide range of solutions that can prevent the degradation of targeted molecules, increase their absorption, uptake and bioavailability. In this work we will present the options currently available concerning micro- and nanodelivery systems for marine lipids; with emphasis on micro/nanoparticles; such as micro/nanocapsules and emulsions. A wide range of bottom-up approaches using casein, chitosan, cyclodextrins, among others; will be discussed. Full article

Marine environment has proven to be a rich source of structurally diverse and complex compounds exhibiting numerous interesting biological effects. Macroalgae are currently being explored as novel and sustainable sources of bioactive compounds for both pharmaceutical and nutraceutical applications. Given the increasing prevalence of different forms of dementia, researchers have been focusing their attention on the discovery and development of new compounds from macroalgae for potential application in neuroprotection. Neuroprotection involves multiple and complex mechanisms, which are deeply related. Therefore, compounds exerting neuroprotective effects through different pathways could present viable approaches in the management of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. In fact, several studies had already provided promising insights into the neuroprotective effects of a series of compounds isolated from different macroalgae species. This review will focus on compounds from macroalgae that exhibit neuroprotective effects and their potential application to treat and/or prevent neurodegenerative diseases. Full article

This study aimed to evaluate the anti-allergic potential of Echium plantagineum L. bee pollen and to characterize its primary metabolites. The activity of E. plantagineum hydromethanolic extract, devoid of alkaloids, was tested against β-hexosaminidase release in rat basophilic leukemic cells (RBL-2H3). Two different stimuli were used: calcium ionophore A23187 and IgE/antigen. Lipoxygenase inhibitory activity was evaluated in a cell-free system using soybean lipoxygenase. Additionally, the extract was analysed by HPLC-UV for organic acids and by GC-IT/MS for fatty acids. In RBL-2H3 cells stimulated either with calcium ionophore or IgE/antigen, the hydromethanolic extract significantly decreased β-hexosaminidase release until the concentration of 2.08 mg/mL, without compromising cellular viability. No effect was found on lipoxygenase. Concerning extract composition, eight organic acids and five fatty acids were determined for the first time. Malonic acid (80%) and α-linolenic acid (27%) were the main compounds in each class. Overall, this study shows promising results, substantiating for the first time the utility of intake of E. plantagineum bee pollen to prevent allergy and ameliorate allergy symptoms, although a potentiation of an allergic response can occur, depending on the dose used. Full article

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. Full article

A monoacylglycerol (1) and a 1:1 mixture of two monogalactosyl diacylglycerols (MGDGs) (2 and 3) were isolated from the brown seaweed Fucus spiralis Linnaeus. The structures were elucidated by spectroscopic means (NMR and MS) and by comparison with the literature. Compound 1 was composed of a glycerol moiety linked to oleic acid (C18:1 Ω9). Compounds 2 and 3 contained a glycerol moiety linked to a galactose unit and eicosapentaenoic acid (C20:5 Ω3) combined with octadecatetraenoic acid (C18:4 Ω3) or linolenic acid (C18:3 Ω3), respectively. The isolated compounds were tested for their cytotoxic and anti-inflammatory activity in RAW 264.7 macrophage cells. All of them inhibited NO production at non-cytotoxic concentrations. The fraction consisting of compounds 2 and 3, in a ratio of 1:1, was slightly more effective than compound 1 (IC₅₀ of 60.06 and 65.70 µg/mL, respectively). To our knowledge, this is the first report of these compounds from F. spiralis and on their anti-inflammatory capacity. Full article

We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the SH-SY5Y cell line being more susceptible. Cell cycle arrest was observed, an effect induced by the sterol, ergosta-7,22-dien-3-ol, present in the extract. Morphological evaluation of treated cells showed the advent of lipid droplets and chromatin condensation compatible with apoptosis, which was confirmed by the evaluation of caspase-3 and -9 activities. Palmitic acid was the main compound responsible for this apoptotic effect by a ceramide-independent mechanism that involved endoplasmic reticulum (ER)-stress with upregulation of CCAAT/-enhancer-binding protein homologous protein (CHOP). Full article

Polyphenols are able to trap free radicals, which contributes to their known antioxidant capacity. In plant extracts, these secondary metabolites may act in concert, in a way that their combined activities will be superior to their individual effects (synergistic interaction). Several polyphenols have demonstrated clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. As so, the intake of these compounds at certain concentrations in the diet and/or supplementation may potentiate the activity of reduced form glutathione (GSH), thus better fighting oxidative stress. The aim of this work was to predict a structure-antioxidant activity relationship using different classes of flavonoids and to assess, for the first time, possible synergisms and antagonisms with GSH. For these purposes a screening microassay involving the scavenging of DPPH^• was applied. In general, among the tested compounds, those lacking the catechol group in B ring showed antagonistic behaviour with GSH. Myricetin displayed additive effect, while quercetin, fisetin, luteolin, luteolin-7-O-glucoside, taxifolin and (+)-catechin demonstrated synergistic actions. Furthermore, adducts formed at C2′ and C5′ of the B ring seem to be more important for the antioxidant capacity than adducts formed at C6 and C8 of the A ring. Full article

Purified phlorotannin extracts from four brown seaweeds (Cystoseira nodicaulis (Withering) M. Roberts, Cystoseira tamariscifolia (Hudson) Papenfuss, Cystoseira usneoides (Linnaeus) M. Roberts and Fucus spiralis Linnaeus), were characterized by HPLC-DAD-ESI-MSⁿ. Fucophloroethol, fucodiphloroethol, fucotriphloroethol, 7-phloroeckol, phlorofucofuroeckol and bieckol/dieckol were identified. The antioxidant activity and the hyaluronidase (HAase) inhibitory capacity exhibited by the extracts were also assessed. A correlation between the extracts activity and their chemical composition was established. F. spiralis, the species presenting higher molecular weight phlorotannins, generally displayed the strongest lipid peroxidation inhibitory activity (IC₅₀ = 2.32 mg/mL dry weight) and the strongest HAase inhibitory capacity (IC₅₀ = 0.73 mg/mL dry weight). As for superoxide radical scavenging, C. nodicaulis was the most efficient species (IC₅₀ = 0.93 mg/mL dry weight), followed by F. spiralis (IC₅₀ = 1.30 mg/mL dry weight). These results show that purified phlorotannin extracts have potent capabilities for preventing and slowing down the skin aging process, which is mainly associated with free radical damage and with the reduction of hyaluronic acid concentration, characteristic of the process. Full article

In this study, the carotenoid profile of the echinoderm Marthasterias glacialis L. was established using HPLC-DAD-APCI-MS/MS equipped with a C₃₀ column. This approach rendered the identification of 20 compounds, eight of them reported for the first time in this marine organism. Differentiation of carotenoid isomers was also achieved. Full article

This study aims to evaluate the antioxidant potential of extracts of Brassica oleracea L. var. acephala DC. (kale) and several materials of Pieris brassicae L., a common pest of Brassica cultures using a cellular model with hamster lung fibroblast (V79 cells) under quiescent conditions and subjected to H₂O₂-induced oxidative stress. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and glutathione was determined by the 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB)-oxidized glutathione (GSSG) reductase recycling assay. The phenolic composition of the extracts was also established by HPLC-DAD. They presented acylated and non acylated flavonoid glycosides, some of them sulfated, and hydroxycinnamic acyl gentiobiosides. All extracts were cytotoxic by themselves at high concentrations and failed to protect V79 cells against H₂O₂ acute toxicity. No relationship between phenolic composition and cytotoxicity of the extracts was found. Rather, a significant increase in glutathione was observed in cells exposed to kale extract, which contained the highest amount and variety of flavonoids. It can be concluded that although flavonoids-rich extracts have the ability to increase cellular antioxidant defenses, the use of extracts of kale and P. brassicae materials by pharmaceutical or food industries, may constitute an insult to health, especially to debilitated individuals, if high doses are consumed. Full article

The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol) isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2), human neuroblastoma (SH-SY5Y), rat basophilic leukemia (RBL-2H3), murine macrophages (RAW.267) and Chinese hamster fibroblasts (V79). Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents. Full article

In recent years, few classes of natural products have received as much attention as phenolics and polyphenols. This special issue of Molecules, “Phenolics and Polyphenolics”, is a remarkable confirmation of this trend. Several aspects related to phenolics chemistry, comprising the several classes, will be discussed. In addition, the increasing interest in phenolics’ biological activities is covered, and several works addressing this matter are referred. Full article

Walnut leaves from nine different cultivars (Arco, Franquette, Hartley, Lara, Marbot, Mayette, Meylannaise, Parisienne and Rego) were studied for their phenolic compounds. Samples were harvested along three consecutive years, at two different geographical locations, in order to evaluate if significant differences in the phenolics composition can be related with genetic, climatic or geographical factors. Nine compounds (3-caffeoylquinic, 3-p-coumaroylquinic and 4-p-coumaroylquinic acids, quercetin 3- galactoside, quercetin 3-arabinoside, quercetin 3-xyloside, quercetin 3-rhamnoside, a quercetin 3-pentoside derivative and a kaempferol 3-pentoside derivative) were quantified using an HPLC-DAD methodology. The qualitative profiles were identical for all samples, but differences were observed in terms of individual compounds’ contents. Multivariate statistical analysis was carried out, showing that significant differences exist among production years, which can be related to climatic reasons. Full article

We report the determination of phenolic compounds in olive leaves by reversed-phase HPLC/DAD, and the evaluation of their in vitro activity against several microorganisms that may be causal agents of human intestinal and respiratory tract infections, namely Gram positive (Bacillus cereus, B. subtilis and Staphylococcus aureus), Gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae) and fungi (Candida albicans and Cryptococcus neoformans). Seven phenolic compounds were identified and quantified: caffeic acid, verbascoside, oleuropein, luteolin 7-O-glucoside, rutin, apigenin 7-O-glucoside and luteolin 4’-O-glucoside. At low concentrations olive leafs extracts showed an unusual combined antibacterial and antifungal action, which suggest their great potential as nutraceuticals, particulalry as a source of phenolic compounds. Full article