Marine Drugs最新文献

Tetrodotoxin (TTX) is a potent marine neurotoxin found in several phylogenetically diverse organisms, some of which are sought as seafood. Since 2015, TTX has been reported in bivalve shellfish from several estuarine locations along the Mediterranean and European Atlantic coasts, posing an emerging food safety concern. Although reports on spatial and temporal distribution have increased in recent years, processes leading to TTX accumulation in European bivalves are yet to be described. Here, we explored the hypothesis that the ribbon worm species Cephalothrix simula, known to contain high levels of TTX, could play a role in the trophic transfer of the toxin into shellfish. During a field study at a single location in southern England, we confirmed C. simula DNA in seawater adjacent to trestle-farmed Pacific oysters Magallana gigas (formerly Crassostrea gigas) with a history of TTX occurrence. C. simula DNA in seawater was significantly higher in June and July during the active phase of toxin accumulation compared to periods of either no or continually decreasing TTX concentrations in M. gigas. In addition, C. simula DNA was detected in oyster digestive glands collected on 15 June 2021, the day with the highest recorded C. simula DNA abundance in seawater. These findings show evidence of a relationship between C. simula and TTX occurrence, providing support for the hypothesis that bivalves may acquire TTX through filter-feeding on microscopic life forms of C. simula present in the water column at particular periods each year. Although further evidence is needed to confirm such feeding activity, this study significantly contributes to discussions about the biological source of TTX in European bivalve shellfish.

This literature review investigated the anti-inflammatory properties of brown algae, emphasizing their potential for dermatological applications. Due to the limitations and side effects associated with corticosteroids and immunomodulators, interest has been growing in harnessing therapeutic qualities from natural products as alternatives to traditional treatments for skin inflammation. This review explored the bioactive compounds in brown algae, specifically looking into two bioactive compounds, namely, fucoidans and phlorotannins, which are widely known to exhibit anti-inflammatory properties. This review synthesized the findings from various studies, highlighting how these compounds can mitigate inflammation by mechanisms such as reducing oxidative stress, inhibiting protein denaturation, modulating immune responses, and targeting inflammatory pathways, particularly in conditions like atopic dermatitis. The findings revealed species-specific variations influenced by the molecular weight and sulphate content. Challenges related to skin permeability were addressed, highlighting the potential of nanoformulations and penetration enhancers to improve delivery. While the in vivo results using animal models provided positive results, further clinical trials are necessary to confirm these outcomes in humans. This review concludes that brown algae hold substantial promise for developing new dermatological treatments and encourages further research to optimize extraction methods, understand the molecular mechanisms, and address practical challenges such as sustainability and regulatory compliance. This review contributes to the growing body of evidence supporting the integration of marine-derived compounds into therapeutic applications for inflammatory skin diseases.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4, a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4, implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

The screening of 166 extracts from tropical marine organisms (invertebrates, macroalgae) and 3 cyclolipopeptides from microorganisms against yeast prions highlighted the potential of Verongiida sponges to prevent the propagation of prions. We isolated the known compounds purealidin Q (1), aplysamine-2 (2), pseudoceratinine A (3), aerophobin-2 (4), aplysamine-1 (5), and pseudoceratinine B (6) for the first time from the Wallisian sponge Suberea laboutei. We then tested compounds 1-6 and sixteen other bromotyrosine and bromophenol derivatives previously isolated from Verongiida sponges against yeast prions, demonstrating the potential of 1-3, 5, 6, aplyzanzine C (7), purealidin A (10), psammaplysenes D (11) and F (12), anomoian F (14), and N,N-dimethyldibromotyramine (15). Following biological tests on mammalian cells, we report here the identification of the hitherto unknown ability of the six bromotyrosine derivatives 1, 2, 5, 7, 11, and 14 of marine origin to reduce the spread of the PrP^Sc prion and the ability of compounds 1 and 2 to reduce endoplasmic reticulum stress. These two biological activities of these bromotyrosine derivatives are, to our knowledge, described here for the first time, offering a new therapeutic perspective for patients suffering from prion diseases that are presently untreatable and consequently fatal.

The first total synthesis of the Australian marine tunicate fungus-derived cyclic peptide talarolide A (1) has confirmed the structure previously proposed on the basis of spectroscopic and chemical analyses and re-affirmed the importance of the unique hydroxamate H-bond bridge in ring conformer stabilization. The unexpected co-synthesis of atrop-talarolide A (8) revealed, for the first time, that hydroxamate H-bond bridging in the talarolide framework invokes non-canonical atropisomerism and that talarolides A (1), C (3), and D (4) all exist naturally as atropisomers. These discoveries raise the intriguing prospect that comparable functionalisation of other cyclic peptides, including those with commercial value, could provide ready access to new "unnatural atropisomeric" chemical space, with new and/or improved chemical and biological properties.

The increasing prevalence of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD), obesity, and type 2 diabetes, poses significant global health challenges. Ketohexokinase (KHK), an enzyme crucial in fructose metabolism, is a potential therapeutic target due to its role in these conditions. This study focused on the discovery of selective KHK inhibitors using in silico methods. We employed structure-based drug design (SBDD) and ligand-based drug design (LBDD) approaches, beginning with molecular docking to identify promising compounds, followed by induced-fit docking (IFD), molecular mechanics generalized Born and surface area continuum solvation (MM-GBSA), and molecular dynamics (MD) simulations to validate binding affinities. Additionally, shape-based screening was conducted to assess structural similarities. The findings highlight several potential inhibitors with favorable ADMET profiles, offering promising candidates for further development in the treatment of fructose-related metabolic disorders.

Here, we report on a bifunctional alginate lyase (Vnalg7) expressed in Pichia pastoris, which can degrade natural Undaria pinnatifida into unsaturated guluronic acid di- and trisaccharide without pretreatment. The enzyme activity of Vnalg7 (3620.00 U/mL-culture) was 15.81-fold higher than that of the original alg (228.90 U/mL-culture), following engineering modification. The degradation rate reached 52.75%, and reducing sugar reached 30.30 mg/mL after combining Vnalg7 (200.00 U/mL-culture) and 14% (w/v) U. pinnatifida for 6 h. Analysis of the action mode indicated that Vnalg7 could degrade many substrates to produce a variety of unsaturated alginate oligosaccharides (AOSs), and the minimal substrate was tetrasaccharide. Site-directed mutagenesis showed that Glu²³⁸, Glu²⁴¹, Glu³¹², Arg²³⁶, His³⁰⁷, Lys⁴¹⁴, and Tyr⁴¹⁸ are essential catalytic sites, while Glu³³⁴, Glu³⁴⁴, and Asp³¹¹ play auxiliary roles. Mechanism analysis revealed the enzymatic degradation pattern of Vnalg7, which mainly recognizes and attacks the third glycosidic linkage from the reducing end of oligosaccharide substrate. Our findings provide a novel alginate lyase tool and a sustainable and commercial production strategy for value-added biomolecules using seaweeds.

Cognitive impairments are frequently reported after ischemic strokes. Novel and effective treatments are required. This study aimed to develop a functional ingredient obtained from marine algae and to determine the effect of the extract on antioxidative stress, as well as neuroprotective effects, in a rat model of MCAO-induced ischemic stroke. Among the selected marine algal extracts, Sargassum polycystum displayed the highest total phenolic content and antioxidative potential, and was subsequently used to evaluate cognitive function in rat models of ischemic stroke. The S. polycystum extract, administered at doses of 100, 300, and 500 mg/kg BW, significantly improved cognitive function by enhancing cognitive performance in the Morris water maze and novel object recognition tests. Biochemical changes revealed that providing S. polycystum increased the activities of SOD, CAT, and GSH-Px by 52.48%, 50.77%, and 66.20%, respectively, and decreased the concentrations of MDA by 51.58% and S100B by 36.64% compared to the vehicle group. These findings suggest that S. polycystum extract may mitigate cognitive impairment in ischemic stroke by reducing oxidative stress and inhibiting S100B expression, thus highlighting its potential as a functional ingredient for drugs and nutraceuticals aimed at neuroprotection.

Fish protein hydrolysates (FPHs) were obtained from different fish sources using a combination of microbial enzymes. The industrially produced FPHs from blue whiting (Micromesistius poutassou) and sprat (Sprattus sprattus) were compared to freeze-dried FPHs generated in-house from hake (Merluccius merluccius) and mackerel (Scomber scombrus) in terms of their physicochemical composition and functionality. Significant differences (p < 0.05) were observed in the protein, moisture, and ash contents of the FPHs, with the majority having high levels of protein (73.24-89.31%). Fractions that were more extensively hydrolysed exhibited a high solubility index (74.05-98.99%) at different pHs. Blue whiting protein hydrolysate-B (BWPH-B) had the highest foaming capacity at pH 4 (146.98 ± 4.28%) and foam stability over 5 min (90-100%) at pH 4, 6, and 8. The emulsifying capacity ranged from 61.11-108.90 m²/g, while emulsion stability was 37.82-76.99% at 0.5% (w/v) concentration. In terms of peptide bioactivity, sprat protein hydrolysate (SPH) had the strongest overall reducing power. The highest Cu²⁺ chelating activity was exhibited by hake protein hydrolysate (HPH) and mackerel protein hydrolysate (MPH), with IC₅₀ values of 0.66 and 0.78 mg protein/mL, respectively, while blue whiting protein hydrolysate-A (BWPH-A) had the highest activity against Fe²⁺ (IC₅₀ = 1.89 mg protein/mL). SPH scavenged DPPH and ABTS radicals best with IC₅₀ values of 0.73 and 2.76 mg protein/mL, respectively. All FPHs displayed noteworthy scavenging activity against hydroxyl radicals, with IC₅₀ values ranging from 0.48-3.46 mg protein/mL. SPH and MPH showed the highest scavenging potential against superoxide radicals with IC₅₀ values of 1.75 and 2.53 mg protein/mL and against hydrogen peroxide with 2.22 and 3.66 mg protein/mL, respectively. While inhibition of α-glucosidase was not observed, the IC₅₀ values against α-amylase ranged from 8.81-18.42 mg protein/mL, with SPH displaying the highest activity. The stability of FPHs following simulated gastrointestinal digestion (SGID) showed an irregular trend. Overall, the findings suggest that marine-derived protein hydrolysates may serve as good sources of natural nutraceuticals with antioxidant and antidiabetic properties.

The aim of the current study is to develop chitosan-based biomaterials which can sustainably release acetylsalicylic acid while presenting significant biological activity. Herein, an innovative ionic bonding strategy between hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and acetylsalicylic acid (AA) was proposed, skillfully utilizing the electrostatic attraction of the ionic bond to achieve the controlled release of drugs. Based on this point, six crosslinked N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan acetylsalicylic acid salt (CHACAA) hydrogel films with varying acetylsalicylic acid contents were prepared by a crosslinking reaction. The results of ¹H nuclear magnetic resonance spectroscopy (¹H NMR) and scanning electron morphology (SEM) confirmed the crosslinked structure, while the obtained hydrogel films possessed favorable thermal stability, mechanical properties, and swelling ability. In addition, the drug release behavior of the hydrogel films was also investigated. As expected, the prepared hydrogel films demonstrated the capability for the sustainable release of acetylsalicylic acid due to ion pair attraction dynamics. Furthermore, the bioactivities of CHACAA-3 and CHACAA-4 hydrogel films with acetylsalicylic acid molar equivalents of 1.25 and 1.5 times those of HACC were particularly pronounced, which not only exhibited an excellent drug sustained-release ability and antibacterial effect, but also had a higher potential for binding and scavenging inflammatory factors, including NO and TNF-α. These findings suggest that CHACAA-3 and CHACAA-4 hydrogel films hold great potential for applications in wound dressing, tissue engineering scaffolds, and drug carriers.