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Mar. Drugs, Volume 21, Issue 4 (April 2023) – 61 articles

Cover Story (view full-size image): Metastatic castration-resistant prostate cancer (mCRPC) cells overexpress proprotein convertase subtilisin/kexin type 9 (PCSK9), contributing to activated motility. The fermentation product pseurotin A (PS) suppressed PCSK9 expression and protein–protein interactions with LDLR. The progression and metastasis of mCRPC in male nude mice fed a high-fat diet showed nearly double tumor volumes, metastasis, serum cholesterol, LDL cholesterol, prostate-specific antigen (PSA), and PCSK9 levels versus mice fed a regular diet. Daily oral PS 10 mg/kg prevented mCRPC locoregional/distant recurrences after primary tumor surgical excision, reduced serum cholesterol, LDL-C, PCSK9 and PSA levels in nude mice. PS is a unique PCSK9-LDLR axis modulator and mCRPC recurrence-suppressive lead. View this paper
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34 pages, 2858 KiB  
Review
Roles of Marine Macroalgae or Seaweeds and Their Bioactive Compounds in Combating Overweight, Obesity and Diabetes: A Comprehensive Review
by S’thandiwe Nozibusiso Magwaza and Md. Shahidul Islam
Mar. Drugs 2023, 21(4), 258; https://doi.org/10.3390/md21040258 - 21 Apr 2023
Cited by 3 | Viewed by 2512
Abstract
Obesity and diabetes are matters of serious concern in the health sector due to their rapid increase in prevalence over the last three decades. Obesity is a severe metabolic problem that results in energy imbalance that is persistent over a long period of [...] Read more.
Obesity and diabetes are matters of serious concern in the health sector due to their rapid increase in prevalence over the last three decades. Obesity is a severe metabolic problem that results in energy imbalance that is persistent over a long period of time, and it is characterized by insulin resistance, suggesting a strong association with type 2 diabetes (T2D). The available therapies for these diseases have side effects and some still need to be approved by the Food and Drug Administration (FDA), and they are expensive for underdeveloped countries. Hence, the need for natural anti-obesity and anti-diabetic drugs has increased in recent years due to their lower costs and having virtually no or negligible side effects. This review thoroughly examined the anti-obesity and anti-diabetic effects of various marine macroalgae or seaweeds and their bioactive compounds in different experimental settings. According to the findings of this review, seaweeds and their bioactive compounds have been shown to have strong potential to alleviate obesity and diabetes in both in vitro and in vivo or animal-model studies. However, the number of clinical trials in this regard is limited. Hence, further studies investigating the effects of marine algal extracts and their bioactive compounds in clinical settings are required for developing anti-obesity and anti-diabetic medicines with better efficacy but lower or no side effects. Full article
(This article belongs to the Section Marine Pharmacology)
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47 pages, 10791 KiB  
Review
Genus Acanthella—A Wealthy Treasure: Secondary Metabolites, Synthesis, Biosynthesis, and Bioactivities
by Sabrin R. M. Ibrahim, Kholoud F. Ghazawi, Samar F. Miski, Duaa Fahad ALsiyud, Shaimaa G. A. Mohamed and Gamal A. Mohamed
Mar. Drugs 2023, 21(4), 257; https://doi.org/10.3390/md21040257 - 21 Apr 2023
Viewed by 3209
Abstract
Marine sponges are multicellular and primitive animals that potentially represent a wealthy source of novel drugs. The genus Acanthella (family Axinellidae) is renowned to produce various metabolites with various structural characteristics and bioactivities, including nitrogen-containing terpenoids, alkaloids, and sterols. The current work provides [...] Read more.
Marine sponges are multicellular and primitive animals that potentially represent a wealthy source of novel drugs. The genus Acanthella (family Axinellidae) is renowned to produce various metabolites with various structural characteristics and bioactivities, including nitrogen-containing terpenoids, alkaloids, and sterols. The current work provides an up-to-date literature survey and comprehensive insight into the reported metabolites from the members of this genus, as well as their sources, biosynthesis, syntheses, and biological activities whenever available. In the current work, 226 metabolites have been discussed based on published data from the period from 1974 to the beginning of 2023 with 90 references. Full article
(This article belongs to the Special Issue Bio-Active Components from Marine Sponges)
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15 pages, 1883 KiB  
Article
Enhanced Molecular Networking Shows Microbacterium sp. V1 as a Factory of Antioxidant Proline-Rich Peptides
by Giovanni Andrea Vitale, Silvia Scarpato, Alfonso Mangoni, Maria Valeria D’Auria, Gerardo Della Sala and Donatella de Pascale
Mar. Drugs 2023, 21(4), 256; https://doi.org/10.3390/md21040256 - 21 Apr 2023
Cited by 3 | Viewed by 2740
Abstract
Two linear proline-rich peptides (12), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium Microbacterium sp. V1, associated with the marine sponge Petrosia ficiformis, collected in the volcanic CO2 vents in Ischia Island (South Italy). Peptide [...] Read more.
Two linear proline-rich peptides (12), bearing an N-terminal pyroglutamate, were isolated from the marine bacterium Microbacterium sp. V1, associated with the marine sponge Petrosia ficiformis, collected in the volcanic CO2 vents in Ischia Island (South Italy). Peptide production was triggered at low temperature following the one strain many compounds (OSMAC) method. Both peptides were detected together with other peptides (38) via an integrated, untargeted MS/MS-based molecular networking and cheminformatic approach. The planar structure of the peptides was determined by extensive 1D and 2D NMR and HR-MS analysis, and the stereochemistry of the aminoacyl residues was inferred by Marfey’s analysis. Peptides 18 are likely to arise from Microbacterium V1 tailor-made proteolysis of tryptone. Peptides 1 and 2 were shown to display antioxidant properties in the ferric-reducing antioxidant power (FRAP) assay. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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20 pages, 1083 KiB  
Article
Preparation and Characterization of a Multicomponent Arthrospira platensis Biomass Hydrolysate with Superior Anti-Hypertensive, Anti-Hyperlipidemic and Antioxidant Activities via Selective Proteolysis
by Cristina Otero and Carlos M. Verdasco-Martín
Mar. Drugs 2023, 21(4), 255; https://doi.org/10.3390/md21040255 - 20 Apr 2023
Cited by 1 | Viewed by 1528
Abstract
Arthrospira platensis biomass is a sustainable source of bioactive products for the food, cosmetic, and medicine industries. As well as primary metabolites, different secondary metabolites can be obtained via distinct enzymatic degradation of biomass. In this work, different hydrophilic extracts were obtained after [...] Read more.
Arthrospira platensis biomass is a sustainable source of bioactive products for the food, cosmetic, and medicine industries. As well as primary metabolites, different secondary metabolites can be obtained via distinct enzymatic degradation of biomass. In this work, different hydrophilic extracts were obtained after treating the biomass with: (i) a serine endo-peptidase (Alcalase®), (ii) a mixture of amino-, dipeptidyl-, and endo-peptidases (Flavourzyme®), (iii) a mixture of endo-1,3(4)-β-glucanase and an endo-1,4-xylanase, and β-glucanase (Ultraflo®), and (iv) an exo-1,3-glucanase (Vinoflow®) (all the enzymes from Novozymes A/S (bagsvaerd, Denmark)); with subsequent extraction of the biocomponents with an isopropanol/hexane mixture. The composition of each aqueous phase extract (in terms of amino acids, peptides, oligo-elements, carbohydrates, and phenols) and their in vitro functional properties were compared. The conditions described in this work using the enzyme Alcalase® permits the extraction of eight distinctive peptides. This extract is 7.3 times more anti-hypertensive, 106 times more anti-hypertriglyceridemic, 26 times more hypocholesterolemic, has 4.4 times more antioxidant activities, and has 2.3 times more phenols, than the extract obtained without any prior enzyme biomass digestion. Alcalase® extract is an advantageous product with potential application in functional food, pharmaceutics, and cosmetics. Full article
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17 pages, 15021 KiB  
Article
A Genomic and Transcriptomic Analysis of the C-Type Lectin Gene Family Reveals Highly Expanded and Diversified Repertoires in Bivalves
by Amaro Saco, Hugo Suárez, Beatriz Novoa and Antonio Figueras
Mar. Drugs 2023, 21(4), 254; https://doi.org/10.3390/md21040254 - 20 Apr 2023
Cited by 6 | Viewed by 1492
Abstract
C-type lectins belong to a widely conserved family of lectins characterized in Metazoa. They show important functional diversity and immune implications, mainly as pathogen recognition receptors. In this work, C-type lectin-like proteins (CTLs) of a set of metazoan species were analyzed, revealing an [...] Read more.
C-type lectins belong to a widely conserved family of lectins characterized in Metazoa. They show important functional diversity and immune implications, mainly as pathogen recognition receptors. In this work, C-type lectin-like proteins (CTLs) of a set of metazoan species were analyzed, revealing an important expansion in bivalve mollusks, which contrasted with the reduced repertoires of other mollusks, such as cephalopods. Orthology relationships demonstrated that these expanded repertoires consisted of CTL subfamilies conserved within Mollusca or Bivalvia and of lineage-specific subfamilies with orthology only between closely related species. Transcriptomic analyses revealed the importance of the bivalve subfamilies in mucosal immunity, as they were mainly expressed in the digestive gland and gills and modulated with specific stimuli. CTL domain-containing proteins that had additional domains (CTLDcps) were also studied, revealing interesting gene families with different conservation degrees of the CTL domain across orthologs from different taxa. Unique bivalve CTLDcps with specific domain architectures were revealed, corresponding to uncharacterized bivalve proteins with putative immune function according to their transcriptomic modulation, which could constitute interesting targets for functional characterization. Full article
(This article belongs to the Special Issue Marine Glycomics 2nd Edition)
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18 pages, 2700 KiB  
Review
Exploring Mycosporine-like Amino Acid UV-Absorbing Natural Products for a New Generation of Environmentally Friendly Sunscreens
by Nedeljka Rosic, Mike Climstein, Glen M. Boyle, Duy Thanh Nguyen and Yunjiang Feng
Mar. Drugs 2023, 21(4), 253; https://doi.org/10.3390/md21040253 - 19 Apr 2023
Cited by 3 | Viewed by 2940
Abstract
Human skin needs additional protection from damaging ultraviolet radiation (UVR: 280–400 nm). Harmful UVR exposure leads to DNA damage and the development of skin cancer. Available sunscreens offer chemical protection from detrimental sun radiation to a certain extent. However, many synthetic sunscreens do [...] Read more.
Human skin needs additional protection from damaging ultraviolet radiation (UVR: 280–400 nm). Harmful UVR exposure leads to DNA damage and the development of skin cancer. Available sunscreens offer chemical protection from detrimental sun radiation to a certain extent. However, many synthetic sunscreens do not provide sufficient UVR protection due to the lack of photostability of their UV-absorbing active ingredients and/or the lack of ability to prevent the formation of free radicals, inevitably leading to skin damage. In addition, synthetic sunscreens may negatively affect human skin, causing irritation, accelerating skin aging and even resulting in allergic reactions. Beyond the potential negative effect on human health, some synthetic sunscreens have been shown to have a harmful impact on the environment. Consequently, identifying photostable, biodegradable, non-toxic, and renewable natural UV filters is imperative to address human health needs and provide a sustainable environmental solution. In nature, marine, freshwater, and terrestrial organisms are protected from harmful UVR through several important photoprotective mechanisms, including the synthesis of UV-absorbing compounds such as mycosporine-like amino acids (MAAs). Beyond MAAs, several other promising, natural UV-absorbing products could be considered for the future development of natural sunscreens. This review investigates the damaging impact of UVR on human health and the necessity of using sunscreens for UV protection, specifically UV-absorbing natural products that are more environmentally friendly than synthetic UV filters. Critical challenges and limitations related to using MAAs in sunscreen formulations are also evaluated. Furthermore, we explain how the genetic diversity of MAA biosynthetic pathways may be linked to their bioactivities and assess MAAs’ potential for applications in human health. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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19 pages, 1869 KiB  
Article
Rugulopteryx-Derived Spatane, Secospatane, Prenylcubebane and Prenylkelsoane Diterpenoids as Inhibitors of Nitric Oxide Production
by Belén Cuevas, Ana I. Arroba, Carolina de los Reyes and Eva Zubía
Mar. Drugs 2023, 21(4), 252; https://doi.org/10.3390/md21040252 - 19 Apr 2023
Cited by 2 | Viewed by 1246
Abstract
This study aimed to evaluate the anti-inflammatory potential of the different classes of diterpenoids produced by algae of the genus Rugulopteryx. First, sixteen diterpenoids (116), including spatane, secospatane, prenylcubebane, and prenylkelsoane metabolites, were isolated from the extract of [...] Read more.
This study aimed to evaluate the anti-inflammatory potential of the different classes of diterpenoids produced by algae of the genus Rugulopteryx. First, sixteen diterpenoids (116), including spatane, secospatane, prenylcubebane, and prenylkelsoane metabolites, were isolated from the extract of the alga Rugulopteryx okamurae collected at the southwestern Spanish coasts. Eight of the isolated diterpenoids are new compounds whose structures were determined by spectroscopic means: the spatanes okaspatols A-D (14); the secospatane rugukamural D (8); the prenylcubebanes okacubols A (13) and B (14); and okamurol A (16), which exhibits an unusual diterpenoid skeleton featuring a kelsoane-type tricyclic nucleus. Second, anti-inflammatory assays were performed on microglial cells Bv.2 and macrophage cells RAW 264.7. Compounds 1, 3, 6, 12, and 16 caused significant inhibition of the NO overproduction induced by LPS in Bv.2 cells, and compounds 3, 5, 12, 14, and 16 significantly decreased levels of NO in LPS-stimulated RAW 264.7 cells. The most active compound was okaspatol C (3), which completely suppressed the effects of LPS stimulation, both in Bv.2 and in RAW 264.7 cells. Full article
(This article belongs to the Special Issue Marine Drugs Research in Spain 2nd Edition)
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12 pages, 2414 KiB  
Article
Harvesting Aurantiochytrium sp. SW1 via Flocculation Using Chitosan: Effects of Flocculation Parameters on Flocculation Efficiency and Zeta Potential
by Nadzirul Zamri, Nurul Nabila Suleiman, Norsyaqira Mohd Johar, Nur Syahidah Mohd Noor, Wei Lun Ang, Nazlina Haiza Mohd Yasin, Yusuf Nazir and Aidil Abdul Hamid
Mar. Drugs 2023, 21(4), 251; https://doi.org/10.3390/md21040251 - 19 Apr 2023
Cited by 1 | Viewed by 1694
Abstract
The use of chitosan as a flocculant has become a topic of interest over the years due to its positively charged polymer and biodegradable and non-toxic properties. However, most studies only focus on microalgae and wastewater treatment. This study provides crucial insight into [...] Read more.
The use of chitosan as a flocculant has become a topic of interest over the years due to its positively charged polymer and biodegradable and non-toxic properties. However, most studies only focus on microalgae and wastewater treatment. This study provides crucial insight into the potential of using chitosan as an organic flocculant to harvest lipids and docosahexaenoic acid (DHA-rich Aurantiochytrium sp. SW1 cells by examining the correlation of flocculation parameters (chitosan concentration, molecular weight, medium pH, culture age, and cell density) toward the flocculation efficiency and zeta potential of the cells. A strong correlation between the pH and harvesting efficiency was observed as the pH increased from 3, with the optimal flocculation efficiency of >95% achieved at a chitosan concentration of 0.5 g/L at pH 6 where the zeta potential was almost zero (3.26 mV). The culture age and chitosan molecular weight have no effect on the flocculation efficiency but increasing the cell density decreases the flocculation efficiency. This is the first study to reveal the potential of chitosan to be used as a harvesting alternative for thraustochytrid cells. Full article
(This article belongs to the Special Issue Marine Thraustochytrids: Biology and Biotechnology)
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15 pages, 9316 KiB  
Article
Development of Novel Pharmaceutical Forms of the Marine Bioactive Pigment Echinochrome A Enabling Alternative Routes of Administration
by Stefanos Kikionis, Paraskevi Papakyriakopoulou, Panagiotis Mavrogiorgis, Elena A. Vasileva, Natalia P. Mishchenko, Sergey A. Fedoreyev, Georgia Valsami, Efstathia Ioannou and Vassilios Roussis
Mar. Drugs 2023, 21(4), 250; https://doi.org/10.3390/md21040250 - 18 Apr 2023
Cited by 1 | Viewed by 2339
Abstract
Echinochrome A (EchA), a marine bioactive pigment isolated from various sea urchin species, is the active agent of the clinically approved drug Histochrome®. EchA is currently only available in the form of an isotonic solution of its di- and tri-sodium salts [...] Read more.
Echinochrome A (EchA), a marine bioactive pigment isolated from various sea urchin species, is the active agent of the clinically approved drug Histochrome®. EchA is currently only available in the form of an isotonic solution of its di- and tri-sodium salts due to its poor water solubility and sensitivity to oxidation. Electrospun polymeric nanofibers have lately emerged as promising drug carriers capable of improving the dissolution and bioavailability of drugs with limited water solubility. In the current study, EchA isolated from sea urchins of the genus Diadema collected at the island of Kastellorizo was incorporated in electrospun micro-/nanofibrous matrices composed of polycaprolactone and polyvinylpyrrolidone in various combinations. The physicochemical properties of the micro-/nanofibers were characterized using SEM, FT-IR, TGA and DSC analyses. The fabricated matrices exhibited variable dissolution/release profiles of EchA, as evidenced in in vitro experiments using gastrointestinal-like fluids (pH 1.2, 4.5 and 6.8). Ex vivo permeability studies using the EchA-loaded micro-/nanofibrous matrices showed an increased permeation of EchA across the duodenum barrier. The results of our study clearly show that electrospun polymeric micro-/nanofibers represent promising carriers for the development of new pharmaceutical formulations with controlled release, as well as increased stability and solubility of EchA, suitable for oral administration, while offering the potential for targeted delivery. Full article
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14 pages, 4547 KiB  
Article
Identification and Functional Analysis of Two Novel Genes—Geranylgeranyl Pyrophosphate Synthase Gene (AlGGPPS) and Isopentenyl Pyrophosphate Isomerase Gene (AlIDI)—from Aurantiochytrium limacinum Significantly Enhance De Novo β-Carotene Biosynthesis in Escherichia coli
by Shitao Shi, Yi Chang, Jinhui Yu, Hui Chen, Qiang Wang and Yuping Bi
Mar. Drugs 2023, 21(4), 249; https://doi.org/10.3390/md21040249 - 17 Apr 2023
Cited by 3 | Viewed by 1575
Abstract
Precursor regulation has been an effective strategy to improve carotenoid production and the availability of novel precursor synthases facilitates engineering improvements. In this work, the putative geranylgeranyl pyrophosphate synthase encoding gene (AlGGPPS) and isopentenyl pyrophosphate isomerase encoding gene (AlIDI) [...] Read more.
Precursor regulation has been an effective strategy to improve carotenoid production and the availability of novel precursor synthases facilitates engineering improvements. In this work, the putative geranylgeranyl pyrophosphate synthase encoding gene (AlGGPPS) and isopentenyl pyrophosphate isomerase encoding gene (AlIDI) from Aurantiochytrium limacinum MYA-1381 were isolated. We applied the excavated AlGGPPS and AlIDI to the de novo β-carotene biosynthetic pathway in Escherichia coli for functional identification and engineering application. Results showed that the two novel genes both functioned in the synthesis of β-carotene. Furthermore, AlGGPPS and AlIDI performed better than the original or endogenous one, with 39.7% and 80.9% increases in β-carotene production, respectively. Due to the coordinated expression of the 2 functional genes, β-carotene content of the modified carotenoid-producing E. coli accumulated a 2.99-fold yield of the initial EBIY strain in 12 h, reaching 10.99 mg/L in flask culture. This study helped to broaden current understanding of the carotenoid biosynthetic pathway in Aurantiochytrium and provided novel functional elements for carotenoid engineering improvements. Full article
(This article belongs to the Special Issue Marine Thraustochytrids: Biology and Biotechnology)
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17 pages, 5461 KiB  
Article
Slipper Limpet (Crepidula fornicata) Shells Support In Vitro Osteogenesis of Human Adipose-Derived Stem Cells
by Arianna De Mori, Umoru Junior Alasa, Alex Mühlhölzl and Gordon Blunn
Mar. Drugs 2023, 21(4), 248; https://doi.org/10.3390/md21040248 - 17 Apr 2023
Cited by 2 | Viewed by 1723
Abstract
This study aimed to investigate a cost-effective alternative to man-made calcium phosphate ceramics for treating bone defects. The slipper limpet is an invasive species in European coastal waters, and its shells composed of calcium carbonate could potentially be a cost-effective source of bone [...] Read more.
This study aimed to investigate a cost-effective alternative to man-made calcium phosphate ceramics for treating bone defects. The slipper limpet is an invasive species in European coastal waters, and its shells composed of calcium carbonate could potentially be a cost-effective source of bone graft substitutes. This research analyzed the mantle of the slipper limpet (Crepidula fornicata) shells to enhance in vitro bone formation. Discs machined from the mantle of C. fornicata were analyzed using scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), X-ray crystallography (XRD), Fourier-transform infrared spectroscopy (FT-IR) and profilometry. Calcium release and bioactivity were also studied. Cell attachment, proliferation, and osteoblastic differentiation (RT-qPCR and alkaline phosphatase activity) were measured in human adipose-derived stem cells grown on the mantle surface. The mantle material was mainly composed of aragonite and showed a sustained Ca2+ release at physiological pH. In addition, apatite formation was observed in simulated body fluid after three weeks, and the materials supported osteoblastic differentiation. Overall, our findings suggest the mantle of C. fornicata shows potential as a material for fabricating bone graft substitutes and structural biomaterials for bone regeneration. Full article
(This article belongs to the Special Issue Marine Bioactive Compounds on Osteoporosis and Related Bone Diseases)
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4 pages, 201 KiB  
Editorial
Marine Natural Products as Anticancer Agents 2.0
by Celso Alves and Marc Diederich
Mar. Drugs 2023, 21(4), 247; https://doi.org/10.3390/md21040247 - 17 Apr 2023
Viewed by 1298
Abstract
Global cancer incidence and death are expected to increase to 28 [...] Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 2.0)
11 pages, 2738 KiB  
Article
Thiolactones and Δ8,9-Pregnene Steroids from the Marine-Derived Fungus Meira sp. 1210CH-42 and Their α-Glucosidase Inhibitory Activity
by Hee Jae Shin, Min Ah Lee, Hwa-Sun Lee and Chang-Su Heo
Mar. Drugs 2023, 21(4), 246; https://doi.org/10.3390/md21040246 - 16 Apr 2023
Cited by 1 | Viewed by 1315
Abstract
The fungal genus Meira was first reported in 2003 and has mostly been found on land. This is the first report of second metabolites from the marine-derived yeast-like fungus Meira sp. One new thiolactone (1), along with one revised thiolactone ( [...] Read more.
The fungal genus Meira was first reported in 2003 and has mostly been found on land. This is the first report of second metabolites from the marine-derived yeast-like fungus Meira sp. One new thiolactone (1), along with one revised thiolactone (2), two new Δ8,9-steroids (4, 5), and one known Δ8,9-steroid (3), were isolated from the Meira sp. 1210CH-42. Their structures were elucidated based on the comprehensive spectroscopic data analysis of 1D, 2D NMR, HR-ESIMS, ECD calculations, and the pyridine-induced deshielding effect. The structure of 5 was confirmed by oxidation of 4 to semisynthetic 5. In the α-glucosidase inhibition assay, compounds 24 showed potent in vitro inhibitory activity with IC50 values of 148.4, 279.7, and 86.0 μM, respectively. Compounds 24 exhibited superior activity as compared to acarbose (IC50 = 418.9 μM). Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi)
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19 pages, 3360 KiB  
Article
Extraction, Structural Characterization, and In Vivo Anti-Inflammatory Effect of Alginate from Cystoseira crinita (Desf.) Borry Harvested in the Bulgarian Black Sea
by Vesela Kokova, Paolina Lukova, Alexandra Baldzhieva, Plamen Katsarov, Cédric Delattre, Roland Molinié, Emmanuel Petit, Redouan Elboutachfaiti, Marianna Murdjeva and Elisaveta Apostolova
Mar. Drugs 2023, 21(4), 245; https://doi.org/10.3390/md21040245 - 16 Apr 2023
Cited by 3 | Viewed by 1881
Abstract
The aim of this study was to identify the chemical composition and sequential structure of alginate isolated from C. crinita harvested in the Bulgarian Black Sea, as well as its effects in histamine-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, [...] Read more.
The aim of this study was to identify the chemical composition and sequential structure of alginate isolated from C. crinita harvested in the Bulgarian Black Sea, as well as its effects in histamine-induced paw inflammation in rats. The serum levels of TNF-α, IL-1β, IL-6, and IL-10 in rats with systemic inflammation, and the levels of TNF-α in a model of acute peritonitis in rats were also investigated. The structural characterization of the polysaccharide was obtained by FTIR, SEC-MALS, and 1H NMR. The extracted alginate had an M/G ratio of 1.018, a molecular weight of 7.31 × 104 g/mol, and a polydispersity index of 1.38. C. crinita alginate in doses of 25 and 100 mg/kg showed well-defined anti-inflammatory activity in the model of paw edema. A significant decrease in serum levels of IL-1β was observed only in animals treated with C. crinita alginate in a dose of 25 mg/kg bw. The concentrations of TNF-α and IL-6 in serum were significantly reduced in rats treated with both doses of the polysaccharide, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. A single dose of alginate did not significantly alter the levels of the pro-inflammatory cytokine TNF-α in the peritoneal fluid of rats with a model of peritonitis. Full article
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25 pages, 1714 KiB  
Article
Gambierone and Sodium Channel Specific Bioactivity Are Associated with the Extracellular Metabolite Pool of the Marine Dinoflagellate Coolia palmyrensis
by Alexander K. Leynse, Elizabeth M. Mudge, Andrew D. Turner, Benjamin H. Maskrey and Alison Robertson
Mar. Drugs 2023, 21(4), 244; https://doi.org/10.3390/md21040244 - 15 Apr 2023
Viewed by 1562
Abstract
Tropical epibenthic dinoflagellate communities produce a plethora of bioactive secondary metabolites, including the toxins ciguatoxins (CTXs) and potentially gambierones, that can contaminate fishes, leading to ciguatera poisoning (CP) when consumed by humans. Many studies have assessed the cellular toxicity of causative dinoflagellate species [...] Read more.
Tropical epibenthic dinoflagellate communities produce a plethora of bioactive secondary metabolites, including the toxins ciguatoxins (CTXs) and potentially gambierones, that can contaminate fishes, leading to ciguatera poisoning (CP) when consumed by humans. Many studies have assessed the cellular toxicity of causative dinoflagellate species to better understand the dynamics of CP outbreaks. However, few studies have explored extracellular toxin pools which may also enter the food web, including through alternative and unanticipated routes of exposure. Additionally, the extracellular exhibition of toxins would suggest an ecological function and may prove important to the ecology of the CP-associated dinoflagellate species. In this study, semi-purified extracts obtained from the media of a Coolia palmyrensis strain (DISL57) isolated from the U.S. Virgin Islands were assessed for bioactivity via a sodium channel specific mouse neuroblastoma cell viability assay and associated metabolites evaluated by targeted and non-targeted liquid chromatography tandem and high-resolution mass spectrometry. We found that extracts of C. palmyrensis media exhibit both veratrine enhancing bioactivity and non-specific bioactivity. LC-HR-MS analysis of the same extract fractions identified gambierone and multiple undescribed peaks with mass spectral characteristics suggestive of structural similarities to polyether compounds. These findings implicate C. palmyrensis as a potential contributor to CP and highlight extracellular toxin pools as a potentially significant source of toxins that may enter the food web through multiple exposure pathways. Full article
(This article belongs to the Special Issue Reef Ecology and Marine Drug Discovery)
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20 pages, 4784 KiB  
Article
Synthesis and Antibiotic Activity of Chitosan-Based Comb-like Co-Polypeptides
by Timothy P. Enright, Dominic L. Garcia, Gia Storti, Jason E. Heindl and Alexander Sidorenko
Mar. Drugs 2023, 21(4), 243; https://doi.org/10.3390/md21040243 - 15 Apr 2023
Viewed by 1393
Abstract
Infections caused by multidrug-resistant Gram-negative bacteria have been named one of the most urgent global health threats due to antimicrobial resistance. Considerable efforts have been made to develop new antibiotic drugs and investigate the mechanism of resistance. Recently, Anti-Microbial Peptides (AMPs) have served [...] Read more.
Infections caused by multidrug-resistant Gram-negative bacteria have been named one of the most urgent global health threats due to antimicrobial resistance. Considerable efforts have been made to develop new antibiotic drugs and investigate the mechanism of resistance. Recently, Anti-Microbial Peptides (AMPs) have served as a paradigm in the design of novel drugs that are active against multidrug-resistant organisms. AMPs are rapid-acting, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs with optimal pharmacodynamics and an ideal selectivity profile. Hence, this work explores the development of novel antimicrobial agents which mimic the structure of graft copolymers and mirror the mode of action of AMPs. A family of polymers comprised of chitosan backbone and AMP side chains were synthesized via the ring-opening polymerization of the N-carboxyanhydride of l-lysine and l-leucine. The polymerization was initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains were explored as drug targets. These graft copolymer systems exhibited activity against clinically significant pathogens and disrupted biofilm formation. Our studies highlight the potential of chitosan-graft-polypeptide structures in biomedical applications. Full article
(This article belongs to the Topic Antimicrobial Agents and Nanomaterials)
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18 pages, 2603 KiB  
Article
Challenging Structure Elucidation of Lumnitzeralactone, an Ellagic Acid Derivative from the Mangrove Lumnitzera racemosa
by Jonas Kappen, Jeprianto Manurung, Tristan Fuchs, Sahithya Phani Babu Vemulapalli, Lea M. Schmitz, Andrej Frolov, Andria Agusta, Alexandra N. Muellner-Riehl, Christian Griesinger, Katrin Franke and Ludger A. Wessjohann
Mar. Drugs 2023, 21(4), 242; https://doi.org/10.3390/md21040242 - 14 Apr 2023
Viewed by 3475
Abstract
The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed [...] Read more.
The previously undescribed natural product lumnitzeralactone (1), which represents a derivative of ellagic acid, was isolated from the anti-bacterial extract of the Indonesian mangrove species Lumnitzera racemosa Willd. The structure of lumnitzeralactone (1), a proton-deficient and highly challenging condensed aromatic ring system, was unambiguously elucidated by extensive spectroscopic analyses involving high-resolution mass spectrometry (HRMS), 1D 1H and 13C nuclear magnetic resonance spectroscopy (NMR), and 2D NMR (including 1,1-ADEQUATE and 1,n-ADEQUATE). Determination of the structure was supported by computer-assisted structure elucidation (CASE system applying ACD-SE), density functional theory (DFT) calculations, and a two-step chemical synthesis. Possible biosynthetic pathways involving mangrove-associated fungi have been suggested. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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16 pages, 11689 KiB  
Article
In Situ Electrospinning of “Dry-Wet” Conversion Nanofiber Dressings for Wound Healing
by Shanfei Liu, Guilin Wu, Wen Wang, Heng Wang, Yingjun Gao and Xuhong Yang
Mar. Drugs 2023, 21(4), 241; https://doi.org/10.3390/md21040241 - 14 Apr 2023
Cited by 4 | Viewed by 1698
Abstract
Rapid wound dressings provide an excellent solution strategy for the treatment of wounds in emergency situations. In this study, aqueous solvent-based PVA/SF/SA/GelMA nanofiber dressings fabricated by a handheld electrospinning device could deposit quickly and directly on the wound, perfectly fitting wounds with various [...] Read more.
Rapid wound dressings provide an excellent solution strategy for the treatment of wounds in emergency situations. In this study, aqueous solvent-based PVA/SF/SA/GelMA nanofiber dressings fabricated by a handheld electrospinning device could deposit quickly and directly on the wound, perfectly fitting wounds with various sizes. Using an aqueous solvent overcame the disadvantage of using the current organic solvents as the medium for rapid wound dressings. The porous dressings had excellent air permeability to ensure smooth gas exchange at the wound site. The distribution range of the tensile strength of the dressings was 9–12 Kpa, and the tensile strain was between 60–80%, providing sufficient mechanical support during wound healing. The dressings could absorb 4–8 times their own weight in solution and could rapidly absorb wound exudates from wet wounds. The nanofibers formed ionic crosslinked hydrogel after absorbing exudates, maintaining the moist condition. It formed a hydrogel–nanofiber composite structure with un-gelled nanofibers and combined the photocrosslinking network to maintain a stable structure at the wound location. The in vitro cell culture assay indicated that the dressings had excellent cell cytocompatibility, and the addition of SF contributed to cell proliferation and wound healing. The in situ deposited nanofiber dressings had excellent potential in the urgent treatment of emergency wounds. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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12 pages, 2403 KiB  
Article
Overexpression of Global Regulator SCrp Leads to the Discovery of New Angucyclines in Streptomyces sp. XS-16
by Xiao Xu, Falei Zhang, Luning Zhou, Yimin Chang, Qian Che, Tianjiao Zhu, Dehai Li and Guojian Zhang
Mar. Drugs 2023, 21(4), 240; https://doi.org/10.3390/md21040240 - 14 Apr 2023
Viewed by 1401
Abstract
Six angucyclines including three unreported compounds (13) were isolated from Streptomyces sp. XS-16 by overexpressing the native global regulator of SCrp (cyclic AMP receptor). The structures were characterized based on nuclear magnetic resonance (NMR) and spectrometry analysis and assisted [...] Read more.
Six angucyclines including three unreported compounds (13) were isolated from Streptomyces sp. XS-16 by overexpressing the native global regulator of SCrp (cyclic AMP receptor). The structures were characterized based on nuclear magnetic resonance (NMR) and spectrometry analysis and assisted by electronic circular dichroism (ECD) calculations. All compounds were tested for their antitumor and antimicrobial activities, and compound 1 showed different inhibitory activities against various tumor cell lines with IC50 values ranging from 0.32 to 5.33 μM. Full article
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4 pages, 187 KiB  
Editorial
Bio-Active Products from Mangrove Ecosystems
by Wenhan Lin, Guoqiang Li and Jing Xu
Mar. Drugs 2023, 21(4), 239; https://doi.org/10.3390/md21040239 - 14 Apr 2023
Cited by 2 | Viewed by 1134
Abstract
Mangrove communities represent the coastal habitats located in intertidal zones or brackish waters of tropical and subtropical coastal areas in over 118 countries [...] Full article
(This article belongs to the Special Issue Bio-Active Products from Mangrove Ecosystems)
14 pages, 17383 KiB  
Article
Physicochemical Properties and Antiherpetic Activity of κ-Carrageenan Complex with Chitosan
by Viktoriya N. Davydova, Natalya V. Krylova, Olga V. Iunikhina, Aleksandra V. Volod’ko, Evgeniya A. Pimenova, Mikhail Y. Shchelkanov and Irina M. Yermak
Mar. Drugs 2023, 21(4), 238; https://doi.org/10.3390/md21040238 - 13 Apr 2023
Cited by 3 | Viewed by 1523
Abstract
Nanoparticles formation is one of the ways to modulate the physicochemical properties and enhance the activity of original polysaccharides. For this purpose, based on the polysaccharide of red algae, κ-carrageenan (κ-CRG), it polyelectrolyte complex (PEC), with chitosan, were obtained. The complex formation was [...] Read more.
Nanoparticles formation is one of the ways to modulate the physicochemical properties and enhance the activity of original polysaccharides. For this purpose, based on the polysaccharide of red algae, κ-carrageenan (κ-CRG), it polyelectrolyte complex (PEC), with chitosan, were obtained. The complex formation was confirmed by ultracentrifugation in a Percoll gradient, with dynamic light scattering. According to electron microscopy and DLS, PEC is dense spherical particles with sizes in the range of 150–250 nm. A decrease in the polydispersity of the initial CRG was detected after the PEC formation. Simultaneous exposure of Vero cells with the studied compounds and herpes simplex virus type 1 (HSV-1) showed that the PEC exhibited significant antiviral activity, effectively inhibiting the early stages of virus–cell interaction. A two-fold increase in the antiherpetic activity (selective index) of PEC compared to κ-CRG was shown, which may be due to a change in the physicochemical characteristics of κ-CRG in PEC. Full article
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10 pages, 1406 KiB  
Communication
Isolation and Characterization of Targeting-HBsAg VNAR Single Domain Antibodies from Whitespotted Bamboo Sharks (Chiloscyllium plagiosum)
by Xierui Jiang, Shan Sun, Zengpeng Li and Mingliang Chen
Mar. Drugs 2023, 21(4), 237; https://doi.org/10.3390/md21040237 - 12 Apr 2023
Cited by 1 | Viewed by 1668
Abstract
Immunoglobulin new antigen receptor (IgNAR) is a naturally occurring antibody that consists of only two heavy chains with two independent variable domains. The variable binding domain of IgNAR, called variable new antigen receptor (VNAR), is attractive due to its solubility, thermal stability, and [...] Read more.
Immunoglobulin new antigen receptor (IgNAR) is a naturally occurring antibody that consists of only two heavy chains with two independent variable domains. The variable binding domain of IgNAR, called variable new antigen receptor (VNAR), is attractive due to its solubility, thermal stability, and small size. Hepatitis B surface antigen (HBsAg) is a viral capsid protein found on the surface of the Hepatitis B virus (HBV). It appears in the blood of an individual infected with HBV and is widely used as a diagnostic marker for HBV infection. In this study, the whitespotted bamboo sharks (Chiloscyllium plagiosum) were immunized with the recombinant HBsAg protein. Peripheral blood leukocytes (PBLs) of immunized bamboo sharks were further isolated and used to construct a VNAR-targeted HBsAg phage display library. The 20 specific VNARs against HBsAg were then isolated by bio-panning and phage ELISA. The 50% of maximal effect (EC50) of three nanobodies, including HB14, HB17, and HB18, were 4.864 nM, 4.260 nM, and 8.979 nM, respectively. The Sandwich ELISA assay further showed that these three nanobodies interacted with different epitopes of HBsAg protein. When taken together, our results provide a new possibility for the application of VNAR in HBV diagnosis and also demonstrate the feasibility of using VNAR for medical testing. Full article
(This article belongs to the Special Issue Antiviral Effects and Molecular Mechanisms of Marine Compounds)
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39 pages, 10698 KiB  
Review
Advances in Natural Products from the Marine-Sponge-Associated Microorganisms with Antimicrobial Activity in the Last Decade
by Jiaqi Liang, Jianglian She, Jun Fu, Jiamin Wang, Yuxiu Ye, Bin Yang, Yonghong Liu, Xuefeng Zhou and Huaming Tao
Mar. Drugs 2023, 21(4), 236; https://doi.org/10.3390/md21040236 - 12 Apr 2023
Cited by 4 | Viewed by 4240
Abstract
Microorganisms are the dominating source of food and nutrition for sponges and play an important role in sponge structure, chemical defense, excretion and evolution. In recent years, plentiful secondary metabolites with novel structures and specific activities have been identified from sponge-associated microorganisms. Additionally, [...] Read more.
Microorganisms are the dominating source of food and nutrition for sponges and play an important role in sponge structure, chemical defense, excretion and evolution. In recent years, plentiful secondary metabolites with novel structures and specific activities have been identified from sponge-associated microorganisms. Additionally, as the phenomenon of the drug resistance of pathogenic bacteria is becoming more and more common, it is urgent to discover new antimicrobial agents. In this paper, we reviewed 270 secondary metabolites with potential antimicrobial activity against a variety of pathogenic strains reported in the literature from 2012 to 2022. Among them, 68.5% were derived from fungi, 23.3% originated from actinomycetes, 3.7% were obtained from other bacteria and 4.4% were discovered using the co-culture method. The structures of these compounds include terpenoids (13%), polyketides (51.9%), alkaloids (17.4%), peptides (11.5%), glucosides (3.3%), etc. Significantly, there are 124 new compounds and 146 known compounds, 55 of which have antifungal activity in addition to antipathogenic bacteria. This review will provide a theoretical basis for the further development of antimicrobial drugs. Full article
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16 pages, 4653 KiB  
Review
Alginate Core-Shell Capsules Production through Coextrusion Methods: Principles and Technologies
by Chanez Bennacef, Sylvie Desobry-Banon, Laurent Probst and Stéphane Desobry
Mar. Drugs 2023, 21(4), 235; https://doi.org/10.3390/md21040235 - 11 Apr 2023
Cited by 4 | Viewed by 2203
Abstract
This paper provides an overview of coextrusion methods for encapsulation. Encapsulation involves the coating or entrapment of a core material such as food ingredients, enzymes, cells, or bioactives. Encapsulation can help compounds add to other matrices, stabilize compounds during storage, or enable controlled [...] Read more.
This paper provides an overview of coextrusion methods for encapsulation. Encapsulation involves the coating or entrapment of a core material such as food ingredients, enzymes, cells, or bioactives. Encapsulation can help compounds add to other matrices, stabilize compounds during storage, or enable controlled delivery. This review explores the principal l coextrusion methods available that can be used to produce core-shell capsules through the use of coaxial nozzles. Four methods for encapsulation by coextrusion are examined in detail, including dripping, jet cutting, centrifugal, and electrohydrodynamic systems. The targeted capsule size determines the appropriate parameters for each method. Coextrusion technology is a promising encapsulation technique able to generate core-shell capsules in a controlled manner, which can be applied to cosmetic, food, pharmaceutical, agriculture, and textile industries. Coextrusion is an excellent way to preserve active molecules and present a significant economic interest. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery 2nd Edition)
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11 pages, 1939 KiB  
Article
Ferroptosis Inhibitory Compounds from the Deep-Sea-Derived Fungus Penicillium sp. MCCC 3A00126
by You-Jia Hao, Zheng-Biao Zou, Ming-Min Xie, Yong Zhang, Lin Xu, Hao-Yu Yu, Hua-Bin Ma and Xian-Wen Yang
Mar. Drugs 2023, 21(4), 234; https://doi.org/10.3390/md21040234 - 10 Apr 2023
Cited by 6 | Viewed by 1638
Abstract
Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (336). The structures of the new compounds were established by spectroscopic data. The absolute configuration of [...] Read more.
Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (336). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC50 values of 5.5 and 3.5 μM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC50 values of 11.6, 7.2, 11.8, and 2.2 μM, respectively. Full article
(This article belongs to the Special Issue Bioactive Compounds from the Deep-Sea-Derived Microorganisms)
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18 pages, 4663 KiB  
Article
Marine Polyether Phycotoxin Palytoxin Induces Apoptotic Cell Death via Mcl-1 and Bcl-2 Downregulation
by Jaemyun Kim, Seungwon Ji, Jin-Young Lee, Jean Lorquin, Barbora Orlikova-Boyer, Claudia Cerella, Aloran Mazumder, Florian Muller, Mario Dicato, Olivier Detournay and Marc Diederich
Mar. Drugs 2023, 21(4), 233; https://doi.org/10.3390/md21040233 - 06 Apr 2023
Cited by 1 | Viewed by 1761
Abstract
Palytoxin is considered one of the most potent biotoxins. As palytoxin-induced cancer cell death mechanisms remain to be elucidated, we investigated this effect on various leukemia and solid tumor cell lines at low picomolar concentrations. As palytoxin did not affect the viability of [...] Read more.
Palytoxin is considered one of the most potent biotoxins. As palytoxin-induced cancer cell death mechanisms remain to be elucidated, we investigated this effect on various leukemia and solid tumor cell lines at low picomolar concentrations. As palytoxin did not affect the viability of peripheral blood mononuclear cells (PBMC) from healthy donors and did not create systemic toxicity in zebrafish, we confirmed excellent differential toxicity. Cell death was characterized by a multi-parametric approach involving the detection of nuclear condensation and caspase activation assays. zVAD-sensitive apoptotic cell death was concomitant with a dose-dependent downregulation of antiapoptotic Bcl-2 family proteins Mcl-1 and Bcl-xL. Proteasome inhibitor MG-132 prevented the proteolysis of Mcl-1, whereas the three major proteasomal enzymatic activities were upregulated by palytoxin. Palytoxin-induced dephosphorylation of Bcl-2 further exacerbated the proapoptotic effect of Mcl-1 and Bcl-xL degradation in a range of leukemia cell lines. As okadaic acid rescued cell death triggered by palytoxin, protein phosphatase (PP)2A was involved in Bcl-2 dephosphorylation and induction of apoptosis by palytoxin. At a translational level, palytoxin abrogated the colony formation capacity of leukemia cell types. Moreover, palytoxin abrogated tumor formation in a zebrafish xenograft assay at concentrations between 10 and 30 pM. Altogether, we provide evidence of the role of palytoxin as a very potent and promising anti-leukemic agent, acting at low picomolar concentrations in cellulo and in vivo. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)
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13 pages, 2726 KiB  
Article
First Report of Two Gymnodimines and Two Tetrodotoxin Analogues in Invertebrates from the North Atlantic Coast of Spain
by Araceli E. Rossignoli, Carmen Mariño, Helena Martín and Juan Blanco
Mar. Drugs 2023, 21(4), 232; https://doi.org/10.3390/md21040232 - 05 Apr 2023
Cited by 4 | Viewed by 1374
Abstract
Gymnodimine D (GYM D), 16-desmethyl gymnodimine D (16-desmethyl GYM D), and two tetrodotoxin analogues have been found in invertebrates obtained from the north Atlantic coast of Spain from May 2021 to October 2022. It is the first report of GYMD and 16-desmethyl GYM [...] Read more.
Gymnodimine D (GYM D), 16-desmethyl gymnodimine D (16-desmethyl GYM D), and two tetrodotoxin analogues have been found in invertebrates obtained from the north Atlantic coast of Spain from May 2021 to October 2022. It is the first report of GYMD and 16-desmethyl GYM D in invertebrates worldwide and of the tetrodotoxin analogues, 5,6,11 trideoxy tetrodotoxin (5,6,11 trideoxy TTX) and its isomer (referred to as 5,6,11 trideoxy-epi-TTX), in the north Atlantic Coast of Spain. In this study, we also report for the first time the detection of tetrodotoxin (TTX) in three species (the cnidaria Calliactis parasitica, an unidentified species, and the bivalve Tellina donacina). The prevalence was medium for GYM D and 16-desmethyl GYM D and low for TTXs overall. The concentrations recorded were variable, with maximum values of GYM D in the bivalve Cerastoderma edule (8.8 μg GYM A equivalents kg−1), of 16-desmethyl GYM D in the bivalve Magellana gigas (10 μg GYM A equivalents kg−1) and of TTX and 5,6,11 trideoxy TTX in the cnidaria C. parasitica (49.7 and 233 μg TTX equivalents kg−1, respectively). There is very scarce information about these compounds. Therefore, the reporting of these new detections will increase the knowledge on the current incidence of marine toxins in Europe that the European Food Safety Authority (EFSA), in particular, and the scientific community, in general, have. This study also highlights the importance of analyzing toxin analogues and metabolites for effective monitoring programs and adequate health protection. Full article
(This article belongs to the Special Issue Novel Methods for Marine Toxins Detection and Quantification 2.0)
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17 pages, 3016 KiB  
Article
Structural Characterization and Anti-Inflammatory Effects of 24-Methylcholesta-5(6), 22-Diene-3β-ol from the Cultured Marine Diatom Phaeodactylum tricornutum; Attenuate Inflammatory Signaling Pathways
by Kalpa W. Samarakoon, Anchala I. Kuruppu, Ju-Young Ko, Ji-Hyeok Lee and You-Jin Jeon
Mar. Drugs 2023, 21(4), 231; https://doi.org/10.3390/md21040231 - 03 Apr 2023
Viewed by 1515
Abstract
In the present investigation, 24-methylcholesta-5(6), 22-diene-3β-ol (MCDO), a major phytosterol was isolated from the cultured marine diatom, Phaeodactylum tricornutum Bohlin, and in vitro and in vivo anti-inflammatory effects were determined. MCDO demonstrated very potent dose-dependent inhibitory effects on the production of nitric oxide [...] Read more.
In the present investigation, 24-methylcholesta-5(6), 22-diene-3β-ol (MCDO), a major phytosterol was isolated from the cultured marine diatom, Phaeodactylum tricornutum Bohlin, and in vitro and in vivo anti-inflammatory effects were determined. MCDO demonstrated very potent dose-dependent inhibitory effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2) against lipopolysaccharide (LPS)-induced RAW 264.7 cells with minimal cytotoxic effects. MCDO also demonstrated a strong and significant suppression of pro-inflammatory cytokines of interleukin-1β (IL-1β) production, but no substantial inhibitory effects were observed on the production of cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) at the tested concentrations against LPS treatment on RAW macrophages. Western blot assay confirmed the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions against LPS-stimulated RAW 264.7 cells. In addition, MCDO was assessed for in vivo anti-inflammatory effects using the zebrafish model. MCDO acted as a potent inhibitor for reactive oxygen species (ROS) and NO levels with a protective effect against the oxidative stress induced by LPS in inflammatory zebrafish embryos. Collectively, MCDO isolated from the cultured marine diatom P. tricornutum exhibited profound anti-inflammatory effects both in vitro and in vivo, suggesting that this major sterol might be a potential treatment for inflammatory diseases. Full article
(This article belongs to the Special Issue Marine Drugs in Cell Signaling Pathways)
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13 pages, 2678 KiB  
Article
A Concise Diastereoselective Total Synthesis of α-Ambrinol
by Josefa L. López-Martínez, Irene Torres-García, Irene Moreno-Gutiérrez, Pascual Oña-Burgos, Antonio Rosales Martínez, Manuel Muñoz-Dorado, Míriam Álvarez-Corral and Ignacio Rodríguez-García
Mar. Drugs 2023, 21(4), 230; https://doi.org/10.3390/md21040230 - 01 Apr 2023
Cited by 1 | Viewed by 1479
Abstract
(−)-cis-α-Ambrinol is a natural product present in ambergris, a substance of marine origin that has been highly valued by perfumers. In this paper, we present a new approach to its total synthesis. The starting material is commercially available α-ionone and the [...] Read more.
(−)-cis-α-Ambrinol is a natural product present in ambergris, a substance of marine origin that has been highly valued by perfumers. In this paper, we present a new approach to its total synthesis. The starting material is commercially available α-ionone and the key step is an intramolecular Barbier-type cyclization induced by CpTiCl2, an organometallic compound prepared in situ by a CpTiCl3 reduction with Mn. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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13 pages, 2838 KiB  
Article
Self-Assembly Nanostructure of Myristoylated ω-Conotoxin MVIIA Increases the Duration of Efficacy and Reduces Side Effects
by Xiufang Ding, Yue Wang, Sida Zhang, Ruihua Zhang, Dong Chen, Long Chen, Yu Zhang, Shi-Zhong Luo, Jianfu Xu and Chengxin Pei
Mar. Drugs 2023, 21(4), 229; https://doi.org/10.3390/md21040229 - 01 Apr 2023
Cited by 3 | Viewed by 1341
Abstract
Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca2+ channels (Cav2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow therapeutic window, [...] Read more.
Chronic pain is one of the most prevalent health problems worldwide. An alternative to suppress or alleviate chronic pain is the use of peptide drugs that block N-type Ca2+ channels (Cav2.2), such as ω-conotoxin MVIIA. Nevertheless, the narrow therapeutic window, severe neurological side effects and low stability associated with peptide MVIIA have restricted its widespread use. Fortunately, self-assembly endows the peptide with high stability and multiple functions, which can effectively control its release to prolong its duration of action. Inspired by this, MVIIA was modified with appropriate fatty acid chains to render it amphiphilic and easier to self-assemble. In this paper, an N-terminal myristoylated MVIIA (Myr-MVIIA, medium carbon chain length) was designed and prepared to undergo self-assembly. The present results indicated that Myr-MVIIA can self-assemble into micelles. Self-assembled micelles formed by Myr-MVIIA at higher concentrations than MVIIA can prolong the duration of the analgesic effect and significantly reduce or even eliminate the side effects of tremor and coordinated motor dysfunction in mice. Full article
(This article belongs to the Special Issue Conotoxin and Conotoxin Analogues: A Pharmacy Cabinet under the Sea)
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