Mar. Drugs, Volume 18, Issue 7 (July 2020) – 40 articles

12-Deacetyl-12-epi-scalaradial, a scalarane sesterterpenoid from a marine sponge Hippospongia sp, has been reported to possess cytotoxic activity on HepG2, MCF-7, and HCT-116 cells. However, there is no research to indicate that 12-deacetyl-12-epi-scalaradial exhibited anticancer effect on cervical cancer HeLa cells. The aim of this study was to investigate the anticancer activity of 12-deacetyl-12-epi-scalaradial against HeLa cells and to explore the mechanism. The results from a methylthiazolyldiphenyl-tetrazolium (MTT) assay suggested that 12-deacetyl-12-epi-scalaradial suppressed the proliferation of HeLa cells and flow cytometry analysis showed 12-deacetyl-12-epi-scalaradial could induce the apoptosis of HeLa cells in dose- and time-dependent manner. Western blotting analysis demonstrated that 12-deacetyl-12-epi-scalaradial triggered apoptosis via mediating the extrinsic pathway and was found to suppress MAPK/ERK pathway which was associate with cancer cell death. Nur77, a critical number of orphan nuclear receptors, plays diverse roles in tumor development as a transcription factor and has been considered as a promising anticancer drug target. The dual-luciferase reporter assays suggested that 12-deacetyl-12-epi-scalaradial could selectively enhance the trans-activation activity of Nur77. Furthermore, Western blotting analysis and fluorescence quenching showed that 12-deacetyl-12-epi-scalaradial could induce the phosphorylation of Nur77 and interact with the ligand-binding domain (LBD) of Nur77. Our research confirmed 12-deacetyl-12-epi-scalaradial as a potential agent for cervical cancer therapy and provided a view that 12-deacetyl-12-epi-scalaradial may be a modulator of Nur77. Full article

Emerging literature suggests that after a stroke, the peri-infarct region exhibits dynamic changes in excitability. In rodent stroke models, treatments that enhance excitability in the peri-infarct cerebral cortex promote motor recovery. This increase in cortical excitability and plasticity is opposed by increases in tonic GABAergic inhibition in the peri-infarct zone beginning three days after a stroke in a mouse model. Maintenance of a favorable excitatory–inhibitory balance promoting cerebrocortical excitability could potentially improve recovery. Brevetoxin-2 (PbTx-2) is a voltage-gated sodium channel (VGSC) gating modifier that increases intracellular sodium ([Na⁺]i), upregulates N-methyl-D-aspartate receptor (NMDAR) channel activity and engages downstream calcium (Ca²⁺) signaling pathways. In immature cerebrocortical neurons, PbTx-2 promoted neuronal structural plasticity by increasing neurite outgrowth, dendritogenesis and synaptogenesis. We hypothesized that PbTx-2 may promote excitability and structural remodeling in the peri-infarct region, leading to improved functional outcomes following a stroke. We tested this hypothesis using epicortical application of PbTx-2 after a photothrombotic stroke in mice. We show that PbTx-2 enhanced the dendritic arborization and synapse density of cortical layer V pyramidal neurons in the peri-infarct cortex. PbTx-2 also produced a robust improvement of motor recovery. These results suggest a novel pharmacologic approach to mimic activity-dependent recovery from stroke. Full article

Polyhydroxylated naphthoquinones (PHNQs), known as spinochromes that can be extracted from sea urchins, are bioactive compounds reported to have medicinal properties and antioxidant activity. The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay showed that pure echinochrome A exhibited a cytotoxic effect on Saos-2 cells in a dose-dependent manner within the test concentration range (15.625–65.5 µg/mL). The PHNQ extract from New Zealand sea urchin Evechinus chloroticus did not induce any cytotoxicity within the same concentration range after 21 days of incubation. Adding calcium chloride (CaCl₂) with echinochrome A increased the number of viable cells, but when CaCl₂ was added with the PHNQs, cell viability decreased. The effect of PHNQs extracted on mineralized nodule formation in Saos-2 cells was investigated using xylenol orange and von Kossa staining methods. Echinochrome A decreased the mineralized nodule formation significantly (p < 0.05), while nodule formation was not affected in the PHNQ treatment group. A significant (p < 0.05) increase in mineralization was observed in the presence of PHNQs (62.5 µg/mL) supplemented with 1.5 mM CaCl₂. In conclusion, the results indicate that PHNQs have the potential to improve the formation of bone mineral phase in vitro, and future research in an animal model is warranted. Full article

In this study, we found that E. prolifera extract (EAEP) exhibits neuroprotective effects in oxidative stress-induced neuronal cells. EAEP improved cell viability as well as attenuated the formation of intracellular reactive oxygen species (ROS) and apoptotic bodies in glutamate-treated hippocampal neuronal cells (HT-22). Furthermore, EAEP improved the expression of brain-derived neurotrophic factor (BDNF) and antioxidant enzymes such as heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase-1 (NQO-1), and glutamate–cysteine ligase catalytic subunit (GCLC) via the tropomyosin-related kinase receptor B/ protein kinase B (TrkB/Akt) signaling pathway. In contrast, the pre-incubation of K252a, a TrkB inhibitor, or MK-2206, an Akt-selective inhibitor, ameliorated the neuroprotective effects of EAEP in oxidative stress-induced neuronal cells. These results suggest that EAEP protects neuronal cells against oxidative stress-induced apoptosis by upregulating the expression of BDNF and antioxidant enzymes via the activation of the TrkB/Akt pathway. In conclusion, such an effect of EAEP, which is rich in carotenoid-derived compounds, may justify its application as a food supplement in the prevention and treatment of neurodegenerative disorders. Full article

There are a large number of fouling organisms in the ocean, which easily attach to the surface of ships, oil platforms and breeding facilities, corrode the surface of equipment, accelerate the aging of equipment, affect the stability and safety of marine facilities and cause serious economic losses. Antifouling coating is an effective method to prevent marine biological fouling. Traditional organic tin and copper oxide coatings are toxic and will contaminate seawater and destroy marine ecology and have been banned or restricted. Environmentally friendly antifouling coatings have become a research hotspot. Among them, the use of natural biological products with antifouling activity as antifouling agents is an important research direction. In addition, some fouling release coatings without antifoulants, biomimetic coatings, photocatalytic coatings and other novel antifouling coatings have also developed rapidly. On the basis of revealing the mechanism of marine biofouling, this paper reviews the latest research strategies to develop environmentally friendly marine antifouling coatings. The composition, antifouling characteristics, antifouling mechanism and effects of various coatings were analyzed emphatically. Finally, the development prospects and future development directions of marine antifouling coatings are forecasted. Full article

Collagen is a promising biomaterial used in the beauty and biomedical industries. In this study, the physicochemical characterization, antioxidant activities, and protective effects against H₂O₂-induced injury of collagen isolated from Acaudina molpadioides were investigated. The amino acid composition analysis showed that the collagen was rich in glycine (Gly), alanine (Ala), and glutamic acid (Glu), but poor in tyrosine (Tyr) and phenylalanine (Phe). Zeta potential analysis revealed that the isoelectric point (pI) of collagen from Acaudina molpadioides was about 4.25. It possessed moderate scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals in a dose-dependent manner. In addition, the collagen was able to effectively improve cell viability and morphology, inhibit the production of Malondialdehyde (MDA), and increase the activities of Superoxide Dismutase (SOD) and Glutathione Peroxidase (GSH-Px) in cultured RAW264.7 cells, resulting in a protective effect against H₂O₂-induced injury. Overall, the results showed that collagen extracted from A. molpadioides has promising prospects in the beauty and cosmetics industries. Full article

A total of 51 sponges (Porifera) and 13 ascidians (Chordata) were collected on the coast of the Yucatan Peninsula (Mexico) and extracted with organic solvents. The resulting extracts were screened for antibacterial activity against four multidrug-resistant (MDR) bacterial pathogens: the Gram-negative Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus. The minimum inhibitory concentrations (MICs) of the organic extracts of each marine organism were determined using a broth microdilution assay. Extracts of eight of the species, in particular the Agelas citrina and Haliclona (Rhizoniera) curacaoensis, displayed activity against some of the pathogens tested. Some of the extracts showed similar MIC values to known antibiotics such as penicillins and aminoglycosides. This study is the first to carry out antimicrobial screening of extracts of marine sponges and ascidians collected from the Yucatan Peninsula. Bioassay-guided fractionation of the active extracts from the sponges Amphimedon compressa and A. citrina displayed, as a preliminary result, that an inseparable mixture of halitoxins and amphitoxins and (-)-agelasine B, respectively, are the major compounds responsible for their corresponding antibacterial activities. This is the first report of the antimicrobial activity of halitoxins and amphitoxins against major multidrug-resistant human pathogens. The promising antibacterial activities detected in this study indicate the coast of Yucatan Peninsula as a potential source of a great variety of marine organisms worthy of further research. Full article

The curiosity and attention that researchers have devoted to alkaloids are due to their bioactivities, structural diversity, and intriguing chemistry. Marine-derived macrocyclic alkaloids (MDMAs) are considered to be a potential source of drugs. Trabectedin, a tetrahydroisoquinoline derivative, has been approved for the treatment of metastatic soft tissue sarcoma and ovarian cancers. MDMAs displayed potent activities that enabled them to be used as anticancer, anti-invasion, antimalarial, antiplasmodial, and antimicrobial. This review presents the reported chemical structures, biological activities, and structure–activity relationships of macrocyclic alkaloids from marine organisms that have been published since their discovery until May 2020. This includes 204 compounds that are categorized under eight subclasses: pyrroles, quinolines, bis-quinolizidines, bis-1-oxaquinolizidines, 3-alkylpiperidines, manzamines, 3-alkyl pyridinium salts, and motuporamines. Full article

The commercial cultivation of microalgae began in the 1960s and Chlorella was one of the first target organisms. The species has long been considered a potential source of renewable energy, an alternative for phytoremediation, and more recently, as a growth and immune stimulant. However, Chlorella vulgaris, which is one of the most studied microalga, has never been comprehensively profiled chemically. In the present study, comprehensive profiling of the Chlorella vulgaris metabolome grown under normal culture conditions was carried out, employing tandem LC-MS/MS to profile the ethanolic extract and GC-MS for fatty acid analysis. The fatty acid profile of C. vulgaris was shown to be rich in omega-6, -7, -9, and -13 fatty acids, with omega-6 being the highest, representing more than sixty percent (>60%) of the total fatty acids. This is a clear indication that this species of Chlorella could serve as a good source of nutrition when incorporated in diets. The profile also showed that the main fatty acid composition was that of C₁₆-C₁₈ (>92%), suggesting that it might be a potential candidate for biodiesel production. LC-MS/MS analysis revealed carotenoid constituents comprising violaxanthin, neoxanthin, lutein, β-carotene, vulgaxanthin I, astaxanthin, and antheraxanthin, along with other pigments such as the chlorophylls. In addition to these, amino acids, vitamins, and simple sugars were also profiled, and through mass spectrometry-based molecular networking, 48 phospholipids were putatively identified. Full article

The geographic position, highly fluctuating sea temperatures and hypersalinity make Persian Gulf an extreme environment. Although this unique environment has high biodiversity dominated by invertebrates, its potential in marine biodiscovery has largely remained untapped. Herein, we aimed at a detailed analysis of the metabolome and bioactivity profiles of the marine sponge Axinella sinoxea collected from the northeast coast of the Persian Gulf in Iran. The crude extract and its Kupchan subextracts were tested in multiple in-house bioassays, and the crude extract and its CHCl₃-soluble portion showed in vitro antibacterial activity against Methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium (Efm). A molecular networking (MN)-based dereplication strategy by UPLC-MS/MS revealed the presence of phospholipids and steroids, while ¹H NMR spectroscopy indicated the presence of additional metabolites, such as diketopiperazines (DKPs). Integrated MN and ¹H NMR analyses on both the crude and CHCl₃ extracts combined with an antibacterial activity-guided isolation approach afforded eight metabolites: a new diketopiperazine, (-)-cyclo(L-trans-Hyp-L-Ile) (8); a known diketopiperazine, cyclo(L-trans-Hyp-L-Phe) (7); two known phospholipids, 1-O-hexadecyl-sn-glycero-3-phosphocholine (1) and 1-O-octadecanoyl-sn-glycero-3-phosphocholine (2); two known steroids, 3β-hydroxycholest-5-ene-7,24-dione (3) and (22E)-3β-hydroxycholesta-5,22-diene-7,24-dione (4); two known monoterpenes, loliolide (5) and 5-epi-loliolide (6). The chemical structures of the isolates were elucidated by a combination of NMR spectroscopy, HRMS and [α]_D analyses. All compounds were tested against MRSA and Efm, and compound 3 showed moderate antibacterial activity against MRSA (IC₅₀ value 70 μg/mL). This is the first study that has dealt with chemical and bioactivity profiling of A. sinoxea leading to isolation and characterization of pure sponge metabolites. Full article

Helicobacter pylori (H. pylori) infection promotes the metastasis of gastric carcinoma cells by modulating signal transduction pathways that regulate cell proliferation, motility, and invasion. Astaxanthin (ASTX), a xanthophyll carotenoid, is known to inhibit cancer cell migration and invasion, however the mechanism of action of ASTX in H. pylori-infected gastric epithelial cells is not well understood. To gain insight into this process, we carried out a comparative RNA sequencing (RNA-Seq) analysis of human gastric cancer AGS (adenocarcinoma gastric) cells as a function of H. pylori infection and ASTX administration. The results were used to identify genes that are differently expressed in response to H. pylori and ASTX. Gene ontology (GO) analysis identified differentially expressed genes (DEGs) to be associated with cell cytoskeleton remodeling, motility, and/or migration. Among the 20 genes identified, those encoding c-MET, PI3KC2, PLCγ1, Cdc42, and ROCK1 were selected for verification by real-time PCR analysis. The verified genes were mapped, using signaling networks contained in the KEGG database, to create a signaling pathway through which ASTX might mitigate the effects of H. pylori-infection. We propose that H. pylori-induced upregulation of the upstream regulator c-MET, and hence, its downstream targets Cdc42 and ROCK1, is suppressed by ASTX. ASTX is also suggested to counteract H. pylori-induced activation of PI3K and PLCγ. In conclusion, ASTX can suppress H. pylori-induced gastric cancer progression by inhibiting cytoskeleton reorganization and reducing cell motility through downregulation of c-MET, EGFR, PI3KC2, PLCγ1, Cdc42, and ROCK1. Full article

Laxaphycins are a family of non-ribosomal lipopeptides that have been isolated from several cyanobacteria. Some of these compounds have presented cytotoxic activities, but their mechanism of action is poorly understood. In this work, the already described laxaphycins B and B3, and acyclolaxaphycins B and B3 were isolated from the marine cyanobacteria Anabaena torulosa. Moreover, two new acyclic compounds, [des-(Ala⁴-Hle⁵)] acyclolaxaphycins B and B3, were purified from the herviborous gastropod Stylocheilus striatus, with this being the first description of biotransformed laxaphycins. The structure of these new compounds was elucidated, together with the absolute configuration of acyclolaxaphycins B and B3. The bioactivities of the six peptides were determined in SH-SY5Y human neuroblastoma cells. Laxaphycins B and B3 were cytotoxic (IC₅₀: 1.8 and 0.8 µM, respectively) through the induction of apoptosis. In comparison, acyclic laxaphycins did not show cytotoxicity but affected mitochondrial functioning, so their effect on autophagy-related protein expression was analyzed, finding that acyclic peptides affected this process by increasing AMPK phosphorylation and inhibiting mTOR. This work confirms the pro-apoptotic properties of cyclic laxaphycins B and is the first report indicating the effects on autophagy of their acyclic analogs. Moreover, gastropod-derived compounds presented ring opening and amino-acids deletion, a biotransformation that had not been previously described. Full article

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes, and mitochondrial dysfunction has been observed in the kidneys of diabetic patients. Tilapia skin peptides (TSPs) are mixtures of small-molecular-weight peptides derived from tilapia skin. Rising evidence suggests that bioactive peptides from marine sources are beneficial for DN. This study aimed to investigate whether TSPs can alleviate the pathological progress in experimental DN by improving mitochondrial dysfunction through the activation of Bnip3/Nix signaling. In the current study, TSPs treatment alleviated the metabolic parameters and renal morphology in streptozotocin-induced diabetic rats. Additionally, TSPs treatment significantly activated Bnip3/Nix signaling and improved the mitochondrial morphology, reversed the over-production of mitochondrial superoxide and cellular reactive oxygen species and the decreased mitochondrial membrane potential, thereby inhibiting the expressions of fibronectin, collagen IV and intercellular cell adhesion molecule-1 in glomerular mesangial cells induced by high glucose. Collectively, our results suggest that TSPs show the renoprotective effect on DN by improving mitochondrial dysfunction, and they can be a potential therapeutic strategy for DN. Full article

Ascidians are marine invertebrates associated with diverse microbial communities, embedded in their tunic, conferring special ecological and biotechnological relevance to these model organisms used in evolutionary and developmental studies. Next-generation sequencing tools have increased the knowledge of ascidians’ associated organisms and their products, but proteomic studies are still scarce. Hence, we explored the tunic of three ascidian species using a shotgun proteomics approach. Proteins extracted from the tunic of Ciona sp., Molgula sp., and Microcosmus sp. were processed using a nano LC-MS/MS system (Ultimate 3000 liquid chromatography system coupled to a Q-Exactive Hybrid Quadrupole-Orbitrap mass spectrometer). Raw data was searched against UniProtKB – the Universal Protein Resource Knowledgebase (Bacteria and Metazoa section) using Proteome Discoverer software. The resulting proteins were merged with a non-redundant Antimicrobial Peptides (AMPs) database and analysed with MaxQuant freeware. Overall, 337 metazoan and 106 bacterial proteins were identified being mainly involved in basal metabolism, cytoskeletal and catalytic functions. 37 AMPs were identified, most of them attributed to eukaryotic origin apart from bacteriocins. These results and the presence of “Biosynthesis of antibiotics” as one of the most highlighted pathways revealed the tunic as a very active tissue in terms of bioactive compounds production, giving insights on the interactions between host and associated organisms. Although the present work constitutes an exploratory study, the approach employed revealed high potential for high-throughput characterization and biodiscovery of the ascidians’ tunic and its microbiome. Full article

Crustins are crustacean cationic cysteine-rich antimicrobial peptides that contain one or two whey acidic protein (WAP) domain(s) at the carboxyl terminus and mainly show antimicrobial and/or proteinase inhibitory activities. Here, we performed genome and transcriptome screening and identified 34 full-length crustin-like encoding genes in Litopenaeus vannamei. Multiple sequence analysis of the deduced mature peptides revealed that these putative crustins included 10 type Ia, two type Ib, one type Ic, 11 type IIa, three type IIb, four type III, one type IV, one type VI, and one type VII. These putative crustins were clustered into different groups. Phylogenetic analysis, considering their domain composition, showed that different types of crustin-like genes in crustaceans might be originated from the WAP core region, along with sequence insertion, duplication, deletion, and amino acid substitution. Tissue distribution analysis suggested that most crustin-like genes were mainly detected in immune-related tissues while several crustin-like genes exhibited tissue-specific expression patterns. Quantitative PCR analysis on 15 selected crustin-like genes showed that most of them were apparently upregulated after Vibrio parahaemolyticus or white spot syndrome virus (WSSV) infection. One type Ib crustin-like gene, mainly expressed in the ovary, showed the highest expression levels before the gastrula stage and was hardly detected after the limb bud stage, suggesting that it was a maternal immune effector. Collectively, the present data revealed the molecular and functional diversity of crustins and their potential evolutionary routes in crustaceans. Full article

Glyceroglycolipids, abundant in cyanobacteria’s photosynthetic membranes, present bioactivities and pharmacological activities, and can be widely used in the pharmaceutical industry. Environmental factors could alter the contents and compositions of cyanobacteria glyceroglycolipids, but the regulation mechanism remains unclear. Therefore, the glyceroglycolipids contents and the transcriptome in Synechococcus elongatus PCC 7942 were analyzed under phosphate starvation. Under phosphate starvation, the decrease of monogalactosyl diacylglycerol (MGDG) and increases of digalactosyl diacylglycerol (DGDG) and sulfoquinovosyl diacylglycerol (SQDG) led to a decrease in the MGDG/DGDG ratio, from 4:1 to 5:3, after 12 days of cultivation. However, UDP–sulfoquinovose synthase gene sqdB, and the SQDG synthase gene sqdX, were down-regulated, and the decreased MGDG/DGDG ratio was later increased back to 2:1 after 15 days of cultivation, suggesting the regulation of glyceroglycolipids on day 12 was based on the MGDG/DGDG ratio maintaining glyceroglycolipid homeostasis. There are 12 differentially expressed transcriptional regulators that could be potential candidates related to glyceroglycolipid regulation, according to the transcriptome analysis. The transcriptome analysis also suggested post-transcriptional or post-translational regulations in glyceroglycolipid synthesis. This study provides further insights into glyceroglycolipid metabolism, as well as the scientific basis for glyceroglycolipid synthesis optimization and cyanobacteria glyceroglycolipids utilization via metabolic engineering. Full article

Seven alkaloidal compounds (2–8) and one polyketide (1) were isolated from a semisolid rice culture of the marine-derived fungus Aspergillus sp. F452. Structures of the isolated compounds were elucidated based on spectroscopic data and comparisons with previously reported data. The alkaloidal compounds (2–8) displayed weak to moderate inhibitory activities against Staphylococcus aureus-derived sortase A (SrtA) without affecting cell viability. Aspermytin A (1) strongly inhibited SrtA activity, with an IC₅₀ value of 146.0 μM, and significantly reduced bacterial adherence to fibronectin-coated surfaces. The present results indicate that the underlying mechanism of action of compound 1 is associated with the inhibition of SrtA-mediated S. aureus adhesion to fibronectin, thus potentially serving as an SrtA inhibitor. Full article

To support the successful application of sponges for water purification and collagen production, we evaluated the effect of depth on sponge morphology, growth, physiology, and functioning. Specimens of Eastern Mediterranean populations of the sponge Chondrosia reniformis (Nardo, 1847) (Demospongiae, Chondrosiida, Chondrosiidae) were reciprocally transplanted between 5 and 20 m depth within the Kaş-Kekova Marine Reserve Area. Control sponges at 5 m had fewer but larger oscula than their conspecifics at 20 m, and a significant inverse relationship between the osculum density and size was found in C. reniformis specimens growing along a natural depth gradient. Sponges transplanted from 20 to 5 m altered their morphology to match the 5 m control sponges, producing fewer but larger oscula, whereas explants transplanted from 5 to 20 m did not show a reciprocal morphological plasticity. Despite the changes in morphology, the clearance, respiration, and growth rates were comparable among all the experimental groups. This indicates that depth-induced morphological changes do not affect the overall performance of the sponges. Hence, the potential for the growth and bioremediation of C. reniformis in mariculture is not likely to change with varying culture depth. The collagen content, however, was higher in shallow water C. reniformis compared to deeper-growing sponges, which requires further study to optimize collagen production. Full article

Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies. ASX reduces inflammation, OS, and apoptosis by regulating different OS pathways though the exact mechanism remains elusive. Based on several studies conducted on type 1 and type 2 DM animal models, orally or parenterally administrated ASX improves insulin resistance and insulin secretion; reduces hyperglycemia; and exerts protective effects against retinopathy, nephropathy, and neuropathy. However, more experimental support is needed to define conditions for its use. Moreover, its efficacy in diabetic patients is poorly explored. In the present review, we aimed to identify the up-to-date biological effects and underlying mechanisms of ASX on the ROS-induced DM-associated metabolic disorders and subsequent complications. The development of an in-depth research to better understand the biological mechanisms involved and to identify the most effective ASX dosage and route of administration is deemed necessary. Full article

Cancer is the main cause of death worldwide, so the discovery of new and effective therapeutic agents must be urgently addressed. Diatoms are rich in minerals and secondary metabolites such as saturated and unsaturated fatty acids, esters, acyl lipids, sterols, proteins, and flavonoids. These bioactive compounds have been reported as potent anti-cancer, anti-oxidant and anti-bacterial agents. Diatoms are unicellular photosynthetic organisms, which are important in the biogeochemical circulation of silica, nitrogen, and carbon, attributable to their short growth-cycle and high yield. The biosilica of diatoms is potentially effective as a carrier for targeted drug delivery in cancer therapy due to its high surface area, nano-porosity, bio-compatibility, and bio-degradability. In vivo studies have shown no significant symptoms of tissue damage in animal models, suggesting the suitability of a diatoms-based system as a safe nanocarrier in nano-medicine applications. This review presents an overview of diatoms’ microalgae possessing anti-cancer activities and the potential role of the diatoms and biosilica in the delivery of anticancer drugs. Diatoms-based antibodies and vitamin B12 as drug carriers are also elaborated. Full article

Chromanols from marine algae are studied for drug development due to its prominent bioactive properties, and mojabanchromanol (MC), a chromanol isolated from a brown algae Sargassum horneri, is found to possess anti-oxidant potential. In this study, we hypothesized MC may attenuate particulate matter (PM)-induced and reactive oxygen species (ROS)-mediated inflammatory responses in airways and tried to identify its potential and underlying mechanism against PM (majority <2.5 µm in diameter)-induced inflammatory responses in a lung type II alveolar epithelial cell line, MLE-12. MC attenuated PM-induced malondialdehyde (MDA), a lipid peroxidation end product, and 8-hydroxydeoxyguanosine (8-OHdG), the most representative DNA oxidative damage product, further validating MC’s potential in attenuating PM-induced oxidative stress. MC also suppressed PM-triggered TLR2/4/7 activation in MLE-12 cells. Moreover, MC reduced ROS-mediated phosphorylation of mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun NH (2)-terminal kinase (JNK) that were also activated in PM exposed cells. MC further inhibited the secretion of pro-inflammatory cytokines (IL-6, IL-1β and IL-33) in MLE-12 cells exposed to PM. These results provide a clear evidence for MC’s potential in attenuating PM-triggered inflammatory responses in MLE-12 cells via repressing TLR2/4/7 and MAPK signaling. Therefore, MC can be developed as a therapeutic agent against PM induced airway inflammatory responses. Full article

Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC₅₀ values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides. Full article

The increment of non-communicable chronic diseases is a constant concern worldwide, with type-2 diabetes mellitus being one of the most common illnesses. A mechanism to avoid diabetes-related hyperglycemia is to reduce food digestion/absorption by using anti-enzymatic (functional) ingredients. This research explored the potential of six common Chilean seaweeds to obtain anti-hyperglycemic polyphenol extracts, based on their capacity to inhibit key enzymes related with starch digestion. Ethanol/water hot pressurized liquid extraction (HPLE), which is an environmentally friendly method, was studied and compared to conventional extraction with acetone. Total polyphenols (TP), antioxidant activity, cytotoxicity and inhibition capacity on α-glucosidase and α-amylase were analyzed. Results showed that the Durvillaea antarctica (cochayuyo) acetone extract had the highest TP content (6.7 ± 0.7 mg gallic acid equivalents (GAE)/g dry seaweed), while its HPLE ethanol/water extract showed the highest antioxidant activity (680.1 ± 11.6 μmol E Trolox/g dry seaweed). No extract affected cell viability significantly. Only cochayuyo produced extracts having relevant anti-enzymatic capacity on both studied enzymes, showing a much stronger inhibition to α-glucosidase (even almost 100% at 1000 µg/mL) than to α-amylase. In conclusion, from the Chilean seaweeds considered in this study, cochayuyo is the most suitable for developing functional ingredients to moderate postprandial glycemic response (starchy foods), since it showed a clear enzymatic inhibition capacity and selectivity. Full article

The marine-derived fungus Aspergillus fumigatus MF071, isolated from sediment collected from the Bohai Sea, China, yielded two new compounds 19S,20-epoxy-18-oxotryprostatin A (1) and 20-hydroxy-18-oxotryprostatin A (2), in addition to 28 known compounds (3–30). The chemical structures were established on the basis of 1D, 2D NMR and HRESIMS spectroscopic data. This is the first report on NMR data of monomethylsulochrin-4-sulphate (4) and pseurotin H (10) as naturally occurring compounds. Compounds 15, 16, 20, 23, and 30 displayed weak antibacterial activity (minimum inhibitory concentration: 100 μg/mL). Compounds 18 and 19 exhibited strong activity against S. aureus (minimum inhibitory concentration: 6.25 and 3.13 μg/mL, respectively) and E. coli (minimum inhibitory concentration: 6.25 and 3.13 μg/mL, respectively). A genomic data analysis revealed the putative biosynthetic gene clusters ftm for fumitremorgins, pso for pseurotins, fga for fumigaclavines, and hel for helvolinic acid. These putative biosynthetic gene clusters fundamentally underpinned the enzymatic and mechanistic function study for the biosynthesis of these compounds. The current study reported two new compounds and biosynthetic gene clusters of fumitremorgins, pseurotins, fumigaclavines and helvolinic acid from Aspergillus fumigatus MF071. Full article

In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX’s ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector. Full article

Chemical study of the CH2Cl2−MeOH (1:1) extract from the sponge Haliclona sp. collected in Mayotte highlighted three new long-chain highly oxygenated polyacetylenes, osirisynes G-I (1–3) together with the known osirisynes A (4), B (5), and E (6). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS and MS/MS data. All compounds were evaluated on catalase and sirtuin 1 activation and on CDK7, proteasome, Fyn kinase, tyrosinase, and elastase inhibition. Five compounds (1; 3–6) inhibited proteasome kinase and two compounds (5–6) inhibited CDK7 and Fyn kinase. Osirisyne B (5) was the most active compound with IC₅₀ on FYNB kinase, CDK7 kinase, and proteasome inhibition of 18.44 µM, 9.13 µM, and 0.26 µM, respectively. Full article

Notably, α-conotoxins with carboxy-terminal (C-terminal) amidation are inhibitors of the pentameric nicotinic acetylcholine receptors (nAChRs), which are therapeutic targets for neurological diseases and disorders. The (α3)₂(β2)₃ nAChR subunit arrangement comprises a pair of α3(+)β2(−) and β2(+)α3(−) interfaces, and a β2(+)β2(−) interface. The β2(+)β2(−) interface has been suggested to have higher agonist affinity relative to the α3(+)β2(−) and β2(+)α3(−) interfaces. Nevertheless, the interactions formed by these subunit interfaces with α-conotoxins are not well understood. Therefore, in order to address this, we modelled the interactions between α-conotoxin LsIA and the α3β2 subtype. The results suggest that the C-terminal carboxylation of LsIA predominantly influenced the enhanced contacts of the conotoxin via residues P7, P14 and C17 on LsIA at the α3(+)β2(−) and β2(+)α3(−) interfaces. However, this enhancement is subtle at the β2(+)β2(−) site, which can compensate the augmented interactions by LsIA at α3(+)β2(−) and β2(+)α3(−) binding sites. Therefore, the divergent interactions at the individual binding interface may account for the minor changes in binding affinity to α3β2 subtype by C-terminal carboxylation of LsIA versus its wild type, as shown in previous experimental results. Overall, these findings may facilitate the development of new drug leads or subtype-selective probes. Full article

Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit p53 expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates p53 and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3’,5,5’-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. Results: Heteronemin inhibited not only expression of proliferative genes and Homo Sapiens Thrombospondin 1 (THBS-1) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-β1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited THBS-1 expression. Moreover, tetrac suppressed TGF-β expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells. Full article

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP⁺) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer’s disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development. Full article

Marine resources have considerable potential to develop high-value materials for applications in different fields, namely pharmaceutical, environmental, and biomedical. Despite that, the lack of solubility of marine-derived polymers in water and common organic solvents could restrict their applications. In the last years, ionic liquids (ILs) have emerged as platforms able to overcome those drawbacks, opening many routes to enlarge the use of marine-derived polymers as biomaterials, among other applications. From this perspective, ILs can be used as an efficient extraction media for polysaccharides from marine microalgae and wastes (e.g., crab shells, squid, and skeletons) or as solvents to process them in different shapes, such as films, hydrogels, nano/microparticles, and scaffolds. The resulting architectures can be applied in wound repair, bone regeneration, or gene and drug delivery systems. This review is focused on the recent research on the applications of ILs as processing platforms of biomaterials derived from marine polymers. Full article