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Mar. Drugs, Volume 22, Issue 4 (April 2024) – 50 articles

Cover Story (view full-size image): Sea anemones are rich sources of bioactive molecules that are vital for therapeutic research due to their varied toxins and antimicrobial peptides. Acid extracts from Actinia equina were tested for antibacterial and antifungal activity, showing promising results with peptide fractions. Further purification via chromatography revealed peptides with broad-spectrum antimicrobial activity, which are effective against various pathogens, including multidrug-resistant strains. These peptides, Equinin A and B, were synthesized and tested in vitro, with Equinin B demonstrating significant antibacterial activity. Its gene structure suggests potential for applied research. Overall, sea anemones offer valuable resources for the development of novel antimicrobial agents with therapeutic potential. View this paper
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14 pages, 2390 KiB  
Article
The Discovery of Weddellamycin, a Tricyclic Polyene Macrolactam Antibiotic from an Antarctic Deep-Sea-Derived Streptomyces sp. DSS69, by Heterologous Expression
by Lu Chen, Kai Liu, Jiali Hong, Zhanzhao Cui, Weijun He, Yemin Wang, Zixin Deng and Meifeng Tao
Mar. Drugs 2024, 22(4), 189; https://doi.org/10.3390/md22040189 - 21 Apr 2024
Viewed by 1069
Abstract
Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by [...] Read more.
Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, Streptomyces sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of wdlA and wdlB and deletion of wdlO. Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10–0.83 μg/mL, and antifungal activity against Candida albicans, with an MIC value of 3.33 μg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC50 values ranging from 2.07 to 11.50 µM. Full article
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15 pages, 2792 KiB  
Article
Characterization of Three Polysaccharide-Based Hydrogels Derived from Laminaria japonica and Their Hemostatic Properties
by Yang Chen, Jinying Shi, Huamai Qiu, Lijun You, Panqi Xu, Rui Rao, Minqian Wu and Ruohan Jia
Mar. Drugs 2024, 22(4), 188; https://doi.org/10.3390/md22040188 - 20 Apr 2024
Viewed by 864
Abstract
Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based [...] Read more.
Three Laminaria japonica polysaccharides (LJPs) extracted via water extraction (LJP-W), acid extraction (LJP-A), and enzymatic extraction (LJP-E) were used as raw materials to be cross-linked with chitosan and polyvinyl alcohol to prepare hydrogels. Compared with conventional hydrogel systems, all three types of LJP-based polysaccharide hydrogels exhibited better swelling properties (14 times their original weight) and the absorption ability of simulated body fluid (first 2 h: 6–10%). They also demonstrated better rigidity and mechanical strength. Young’s modulus of LJP-E was 4 times that of the blank. In terms of hemostatic properties, all three polysaccharide hydrogels did not show significant cytotoxic and hemolytic properties. The enzyme- and acid-extracted hydrogels (LJP-Gel-A and LJP-Gel-E) demonstrated better whole-blood coagulant ability compared with the water-extracted hydrogel (LJP-Gel-W), as evidenced by the whole blood coagulation index being half that of LJP-Gel-W. Additionally, the lactate dehydrogenase viabilities of LJP-Gel-A and LJP-Gel-E were significantly higher, at about four and three times those of water extraction, respectively. The above results suggested that LJP-Gel-A and LJP-Gel-E exhibited better blood coagulation capabilities than LJP-Gel-W, due to their enhanced platelet enrichment and adhesion properties. Consequently, these hydrogels are more conducive to promoting coagulation and have good potential for wound hemostasis. Full article
(This article belongs to the Special Issue Bioactive Polysaccharides from Seaweeds)
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14 pages, 2983 KiB  
Article
Exploring the Hypocholesterolemic Potential of a Fucus vesiculosus Extract: Omic Insights into Molecular Mechanisms at the Intestinal Level
by Rebeca André, Rita Pacheco, Hugo M. Santos and Maria Luísa Serralheiro
Mar. Drugs 2024, 22(4), 187; https://doi.org/10.3390/md22040187 - 20 Apr 2024
Viewed by 1206
Abstract
High blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect [...] Read more.
High blood cholesterol levels are a major risk factor for cardiovascular diseases. A purified aqueous extract of Fucus vesiculosus, rich in phlorotannins and peptides, has been described for its potential to inhibit cholesterol biosynthesis and intestinal absorption. In this work, the effect of this extract on intestinal cells’ metabolites and proteins was analysed to gain a deeper understanding of its mode of action on lipids’ metabolism, particularly concerning the absorption and transport of exogenous cholesterol. Caco-2 cells, differentiated into enterocytes, were exposed to the extract, and analysed by untargeted metabolomics and proteomics. The results of the metabolomic analysis showed statistically significant differences in glutathione content of cells exposed to the extract compared to control cells, along with an increased expression of fatty acid amides in exposed cells. A proteomic analysis showed an increased expression in cells exposed to the extract compared to control cells of FAB1 and NPC1, proteins known to be involved in lipid metabolism and transport. To the extent of our knowledge, this study is the first use of untargeted metabolomics and a proteomic analysis to investigate the effects of F. vesiculosus on differentiated Caco-2 cells, offering insights into the molecular mechanism of the extract’s compounds on intestinal cells. Full article
(This article belongs to the Special Issue Marine-Derived Compounds Applied in Cardiovascular Disease)
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9 pages, 2990 KiB  
Communication
Cytotoxic and Antibacterial Meroterpenoids Isolated from the Marine-Derived Fungus Talaromyces sp. M27416
by Lingzhi Tang, Jinmei Xia, Zhongwei Chen, Fengjiao Lin, Zongze Shao, Weiyi Wang and Xuan Hong
Mar. Drugs 2024, 22(4), 186; https://doi.org/10.3390/md22040186 - 20 Apr 2024
Viewed by 755
Abstract
Three novel meroterpenoids, taladrimanins B–D (13), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds (46). We delineated taladrimanin B’s (1) structure using HRESIMS and NMR, confirmed its [...] Read more.
Three novel meroterpenoids, taladrimanins B–D (13), were isolated from the marine-derived fungus Talaromyces sp. M27416, alongside three biogenetically related compounds (46). We delineated taladrimanin B’s (1) structure using HRESIMS and NMR, confirmed its configuration via quantum chemical NMR analysis and DP4+ methodology, and verified it through X-ray crystallography. ECD calculations determined the absolute configuration of compound 1, while comparative NMR and ECD analyses elucidated the absolute configurations of 2 and 3. These compounds are drimane-type meroterpenoids with a C10 polyketide unit (8R-configuration). We proposed a biosynthetic pathway and noted that compound 1 showed cytotoxic activity against MKN-45 and 5637 cell lines and selective antibacterial effects against Staphylococcus aureus CICC 10384. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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15 pages, 3281 KiB  
Article
Zeaxanthin epoxidase 3 Knockout Mutants of the Model Diatom Phaeodactylum tricornutum Enable Commercial Production of the Bioactive Carotenoid Diatoxanthin
by Cecilie Græsholt, Tore Brembu, Charlotte Volpe, Zdenka Bartosova, Manuel Serif, Per Winge and Marianne Nymark
Mar. Drugs 2024, 22(4), 185; https://doi.org/10.3390/md22040185 - 19 Apr 2024
Viewed by 1049
Abstract
Carotenoids are pigments that have a range of functions in human health. The carotenoid diatoxanthin is suggested to have antioxidant, anti-inflammatory and chemo-preventive properties. Diatoxanthin is only produced by a few groups of microalgae, where it functions in photoprotection. Its large-scale production in [...] Read more.
Carotenoids are pigments that have a range of functions in human health. The carotenoid diatoxanthin is suggested to have antioxidant, anti-inflammatory and chemo-preventive properties. Diatoxanthin is only produced by a few groups of microalgae, where it functions in photoprotection. Its large-scale production in microalgae is currently not feasible. In fact, rapid conversion into the inactive pigment diadinoxanthin is triggered when cells are removed from a high-intensity light source, which is the case during large-scale harvesting of microalgae biomass. Zeaxanthin epoxidase (ZEP) 2 and/or ZEP3 have been suggested to be responsible for the back-conversion of high-light accumulated diatoxanthin to diadinoxanthin in low-light in diatoms. Using CRISPR/Cas9 gene editing technology, we knocked out the ZEP2 and ZEP3 genes in the marine diatom Phaeodactylum tricornutum to investigate their role in the diadinoxanthin–diatoxanthin cycle and determine if one of the mutant strains could function as a diatoxanthin production line. Light-shift experiments proved that ZEP3 encodes the enzyme converting diatoxanthin to diadinoxanthin in low light. Loss of ZEP3 caused the high-light-accumulated diatoxanthin to be stable for several hours after the cultures had been returned to low light, suggesting that zep3 mutant strains could be suitable as commercial production lines of diatoxanthin. Full article
(This article belongs to the Special Issue Marine Anti-inflammatory and Antioxidant Agents 3.0)
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19 pages, 3351 KiB  
Article
Chemical Synthesis of Fucosylated Chondroitin Sulfate Tetrasaccharide with Fucosyl Branch at the 6-OH of GalNAc Residue
by Changlun Lv, Xiaona Li, Guoqing Yang, Haijiao Chen and Chunxia Li
Mar. Drugs 2024, 22(4), 184; https://doi.org/10.3390/md22040184 - 19 Apr 2024
Viewed by 679
Abstract
Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH [...] Read more.
Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure–activity relationship in the future. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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11 pages, 2148 KiB  
Article
Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells
by Jie Wang, Yue-Lu Yan, Xin-Yi Yu, Jia-Yan Pan, Xin-Lian Liu, Li-Li Hong and Bin Wang
Mar. Drugs 2024, 22(4), 183; https://doi.org/10.3390/md22040183 - 19 Apr 2024
Viewed by 786
Abstract
Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their [...] Read more.
Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 24 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 μM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial–mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT. Full article
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34 pages, 4201 KiB  
Review
Statistical Tools to Optimize the Recovery of Bioactive Compounds from Marine Byproducts
by Zenebe Tadesse Tsegay, Sofia Agriopoulou, Moufida Chaari, Slim Smaoui and Theodoros Varzakas
Mar. Drugs 2024, 22(4), 182; https://doi.org/10.3390/md22040182 - 18 Apr 2024
Cited by 1 | Viewed by 2161
Abstract
Techniques for extracting important bioactive molecules from seafood byproducts, viz., bones, heads, skin, frames, fins, shells, guts, and viscera, are receiving emphasis due to the need for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is [...] Read more.
Techniques for extracting important bioactive molecules from seafood byproducts, viz., bones, heads, skin, frames, fins, shells, guts, and viscera, are receiving emphasis due to the need for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could enable these improvements. In this review, statistical optimization strategies applied for the extraction process parameters of obtaining bioactive molecules from seafood byproducts are focused upon. The type of experimental designs and techniques applied to criticize and validate the effects of independent variables on the extraction output are addressed. Dominant parameters studied were the enzyme/substrate ratio, pH, time, temperature, and power of extraction instruments. The yield of bioactive compounds, including long-chain polyunsaturated fatty acids, amino acids, peptides, enzymes, gelatine, collagen, chitin, vitamins, polyphenolic constituents, carotenoids, etc., were the most studied responses. Efficiency and/or economic and quality considerations and their selected optimization strategies that favor the production of potential bioactive molecules were also reviewed. Full article
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11 pages, 3393 KiB  
Article
Discovery of a Novel Chromone Enantiomer and the Precursors of Nonactic Acid from the Coral-Reef-Derived Streptomyces sp. SCSIO 66814
by Wenping Ding, Yanqun Li, Xingyu Li, Jiajia Yin, Songbiao Shi, Xinpeng Tian, Si Zhang and Hao Yin
Mar. Drugs 2024, 22(4), 181; https://doi.org/10.3390/md22040181 - 17 Apr 2024
Viewed by 661
Abstract
Three pairs of enantiomers (13)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (57) were [...] Read more.
Three pairs of enantiomers (13)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (57) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 25, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals. Full article
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28 pages, 5918 KiB  
Review
Marine-Derived Metabolites Act as Promising Antifungal Agents
by Sijin Hang, Hui Lu and Yuanying Jiang
Mar. Drugs 2024, 22(4), 180; https://doi.org/10.3390/md22040180 - 17 Apr 2024
Viewed by 880
Abstract
The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, and echinocandins, face increasing resistance from pathogenic fungi. Therefore, there is a pressing [...] Read more.
The incidence of invasive fungal diseases (IFDs) is on the rise globally, particularly among immunocompromised patients, leading to significant morbidity and mortality. Current clinical antifungal agents, such as polyenes, azoles, and echinocandins, face increasing resistance from pathogenic fungi. Therefore, there is a pressing need for the development of novel antifungal drugs. Marine-derived secondary metabolites represent valuable resources that are characterized by varied chemical structures and pharmacological activities. While numerous compounds exhibiting promising antifungal activity have been identified, a comprehensive review elucidating their specific underlying mechanisms remains lacking. In this review, we have compiled a summary of antifungal compounds derived from marine organisms, highlighting their diverse mechanisms of action targeting various fungal cellular components, including the cell wall, cell membrane, mitochondria, chromosomes, drug efflux pumps, and several biological processes, including vesicular trafficking and the growth of hyphae and biofilms. This review is helpful for the subsequent development of antifungal drugs due to its summary of the antifungal mechanisms of secondary metabolites from marine organisms. Full article
(This article belongs to the Topic Antimicrobial Agents and Nanomaterials)
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17 pages, 1430 KiB  
Article
Effect of Post-Extraction Ultrasonication on Compositional Features and Antioxidant Activities of Enzymatic/Alkaline Extracts of Palmaria palmata
by Sakhi Ghelichi, Ann-Dorit Moltke Sørensen, Mona Hajfathalian and Charlotte Jacobsen
Mar. Drugs 2024, 22(4), 179; https://doi.org/10.3390/md22040179 - 17 Apr 2024
Viewed by 1290
Abstract
Palmaria palmata is a viable source of nutrients with bioactive properties. The present study determined the potential role of post-extraction ultrasonication on some compositional features and antioxidant properties of enzymatic/alkaline extracts of P. palmata (EAEP). No significant difference was detected in terms of [...] Read more.
Palmaria palmata is a viable source of nutrients with bioactive properties. The present study determined the potential role of post-extraction ultrasonication on some compositional features and antioxidant properties of enzymatic/alkaline extracts of P. palmata (EAEP). No significant difference was detected in terms of protein content and recovery, as well as the amino acid composition of the extracts. The nitrogen-to-protein conversion factor of 5 was found to be too high for the seaweed and EAEP. The extracts sonicated by bath for 10 min and not sonicated showed the highest and lowest total phenolic contents (p < 0.05), respectively. The highest radical scavenging and lowest metal-chelating activities were observed for the non-sonicated sample, as evidenced by IC50 values. The extract sonicated by bath for 10 min showed the most favorable in vitro antioxidant properties since its radical scavenging was not significantly different from that of the not-sonicated sample (p > 0.05). In contrast, its metal-chelating activity was significantly higher (p < 0.05). To conclude, post-extraction ultrasonication by an ultrasonic bath for 10 min is recommended to increase phenolic content and improve the antioxidant properties of EAEP. Full article
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15 pages, 1834 KiB  
Article
Pharmacokinetics and Safety of Lurbinectedin Administrated with Itraconazole in Cancer Patients: A Drug–Drug Interaction Study
by Irene Moreno, Tatiana Hernández, Emiliano Calvo, Salvador Fudio, Carmen Kahatt, Sara Martínez, Jorge Luis Iglesias, Román Octavio Calafati, Laura Pérez-Ramos, Lola Montilla, Ali Zeaiter and Rubin Lubomirov
Mar. Drugs 2024, 22(4), 178; https://doi.org/10.3390/md22040178 - 16 Apr 2024
Viewed by 914
Abstract
This open-label, two-part, phase Ib drug–drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, [...] Read more.
This open-label, two-part, phase Ib drug–drug interaction study investigated whether the pharmacokinetic (PK) and safety profiles of lurbinectedin (LRB), a marine-derived drug, are affected by co-administration of itraconazole (ITZ), a strong CYP3A4 inhibitor, in adult patients with advanced solid tumors. In Part A, three patients were sequentially assigned to Sequence 1 (LRB 0.8 mg/m2, 1-h intravenous [IV] + ITZ 200 mg/day oral in Cycle 1 [C1] and LRB alone 3.2 mg/m2, 1 h, IV in Cycle 2 [C2]). In Part B, 11 patients were randomized (1:1) to receive either Sequence 1 (LRB at 0.9 mg/m2 + ITZ in C1 and LRB alone in C2) or Sequence 2 (LRB alone in C1 and LRB + ITZ in C2). Eleven patients were evaluable for PK analysis: three in Part A and eight in Part B (four per sequence). The systemic total exposure of LRB increased with ITZ co-administration: 15% for Cmax, area under the curve (AUC) 2.4-fold for AUC0–t and 2.7-fold for AUC0–∞. Co-administration with ITZ produced statistically significant modifications in the unbound plasma LRB PK parameters. The LRB safety profile was consistent with the toxicities described in previous studies. Co-administration with multiple doses of ITZ significantly altered LRB systemic exposure. Hence, to avoid LRB overexposure when co-administered with strong CYP3A4 inhibitors, an LRB dose reduction proportional to CL reduction should be applied. Full article
(This article belongs to the Section Marine Pharmacology)
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14 pages, 3516 KiB  
Article
2,3-Dimethoxycinnamic Acid from a Marine Actinomycete, a Promising Quorum Sensing Inhibitor in Chromobacterium violaceum
by Yanqun Li, Wenping Ding, Jiajia Yin, Xingyu Li, Xinpeng Tian, Zhihui Xiao, Fazuo Wang and Hao Yin
Mar. Drugs 2024, 22(4), 177; https://doi.org/10.3390/md22040177 - 16 Apr 2024
Viewed by 817
Abstract
An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated [...] Read more.
An ethyl acetate extract of a marine actinomycete strain, Nocardiopsis mentallicus SCSIO 53858, isolated from a deep-sea sediment sample in the South China Sea, exhibited anti-quorum-sensing (QS) activity against Chromobacterium violaceum CV026. Guided by the anti-QS activity, a novel active compound was isolated and purified from the extract and was identified as 2,3-dimethoxycinnamic acid (2,3-DCA) through spectral data analysis. At a concentration of 150 μg/mL, 2,3-DCA exhibited robust inhibitory effects on three QS-regulated traits of C. violaceum CV026: violacein production, swarming motility, and biofilm formation, with inhibition rates of 73.9%, 65.9%, and 37.8%, respectively. The quantitative reverse transcription polymerase chain reaction results indicated that 2,3-DCA can disrupt the QS system in C. violaceum CV026 by effectively suppressing the expression of QS-related genes, including cviR, vioA, vioB, and vioE. Molecular docking analysis revealed that 2,3-DCA hinders the QS system by competitively binding to the same binding pocket on the CviR receptor as the natural signal molecule N-hexanoyl-L-homoserine lactone. Collectively, these findings suggest that 2,3-DCA exhibits promising potential as an inhibitor of QS systems, providing a potential solution to the emerging problem of bacterial resistance. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
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14 pages, 1389 KiB  
Article
Automated Patch Clamp for the Detection of Tetrodotoxin in Pufferfish Samples
by Mònica Campàs, Jaume Reverté, Àngels Tudó, Mounira Alkassar, Jorge Diogène and Francesc X. Sureda
Mar. Drugs 2024, 22(4), 176; https://doi.org/10.3390/md22040176 - 15 Apr 2024
Viewed by 793
Abstract
Tetrodotoxin (TTX) is a marine toxin responsible for many intoxications around the world. Its presence in some pufferfish species and, as recently reported, in shellfish, poses a serious health concern. Although TTX is not routinely monitored, there is a need for fast, sensitive, [...] Read more.
Tetrodotoxin (TTX) is a marine toxin responsible for many intoxications around the world. Its presence in some pufferfish species and, as recently reported, in shellfish, poses a serious health concern. Although TTX is not routinely monitored, there is a need for fast, sensitive, reliable, and simple methods for its detection and quantification. In this work, we describe the use of an automated patch clamp (APC) system with Neuro-2a cells for the determination of TTX contents in pufferfish samples. The cells showed an IC50 of 6.4 nM for TTX and were not affected by the presence of muscle, skin, liver, and gonad tissues of a Sphoeroides pachygaster specimen (TTX-free) when analysed at 10 mg/mL. The LOD achieved with this technique was 0.05 mg TTX equiv./kg, which is far below the Japanese regulatory limit of 2 mg TTX equiv./kg. The APC system was applied to the analysis of extracts of a Lagocephalus sceleratus specimen, showing TTX contents that followed the trend of gonads > liver > skin > muscle. The APC system, providing an in vitro toxicological approach, offers the advantages of being sensitive, rapid, and reliable for the detection of TTX-like compounds in seafood. Full article
(This article belongs to the Special Issue Marine Biotoxins 3.0)
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17 pages, 15384 KiB  
Article
Ethanol Extract of Limonium bicolor Improves Dextran Sulfate Sodium-Induced Ulcerative Colitis by Alleviating Inflammation and Restoring Gut Microbiota Dysbiosis in Mice
by Wei Jia, Siyu Yu, Xi Liu, Qingqing Le, Xiwen He, Lutao Yu, Jianlin He, Longhe Yang and Huiyuan Gao
Mar. Drugs 2024, 22(4), 175; https://doi.org/10.3390/md22040175 - 15 Apr 2024
Viewed by 954
Abstract
Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor [...] Read more.
Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor (LB), an aquatic traditional Chinese medicine (TCM), exerts multi-targeted therapeutic effects with few side effects and is used to treat anemia and hemostasis. Nevertheless, the impact of LB on UC and its mechanism of action remain unclear. Therefore, the objective of this study was to investigate the anti-inflammatory effects and mechanism of action of ethanol extract of LB (LBE) in lipopolysaccharide-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced UC. The results showed that LBE suppressed the secretion of cytokines in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. LBE had protective effects against DSS-induced colitis in mice, decreased the disease activity index (DAI) score, alleviated symptoms, increased colon length, and improved histological characteristics, thus having protective effects against DSS-induced colitis in mice. In addition, it reversed disturbances in the abundance of proteobacteria and probiotics such as Lactobacillus and Blautia in mice with DSS-induced UC. Based on the results of network pharmacology analysis, we identified four main compounds in LBE that are associated with five inflammatory genes (Ptgs2, Plg, Ppar-γ, F2, and Gpr35). These results improve comprehension of the biological activity and functionality of LB and may facilitate the development of LB-based compounds for the treatment of UC. Full article
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16 pages, 3702 KiB  
Article
Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation
by Jiaxi Chen, Jieping Zhang, Lijuan Cai, Li Guo, Zhenyu Cai, Hua Han and Wen Zhang
Mar. Drugs 2024, 22(4), 174; https://doi.org/10.3390/md22040174 - 13 Apr 2024
Viewed by 838
Abstract
Cholestane-3β,5α,6β-triol (CT) and its analogues are abundant in natural sources and are reported to demonstrate cytotoxicity toward different kinds of tumor cells without a deep probe into their mechanism of action. CT is also one of the major metabolic oxysterols of cholesterol in [...] Read more.
Cholestane-3β,5α,6β-triol (CT) and its analogues are abundant in natural sources and are reported to demonstrate cytotoxicity toward different kinds of tumor cells without a deep probe into their mechanism of action. CT is also one of the major metabolic oxysterols of cholesterol in mammals and is found to accumulate in various diseases. An extensive exploration of the biological roles of CT over the past few decades has established its identity as an apoptosis inducer. In this study, the effects of CT on A549 cell death were investigated through cell viability assays. RNA-sequencing analysis and western blot of CT-treated A549 cells revealed the role of CT in inducing endoplasmic reticulum (ER) stress response and enhancing autophagy flux, suggesting a putative mechanism of CT-induced cell-death activation involving reactive oxygen species (ROS)-mediated ER stress and autophagy. It is reported for the first time that the upregulation of autophagy induced by CT can serve as a cellular cytotoxicity response in accelerating CT-induced cell death in A549 cells. This research provides evidence for the effect of CT as an oxysterol in cell response to oxidative damage and allows for a deep understanding of cholesterol in its response in an oxidative stress environment that commonly occurs in the progression of various diseases. Full article
(This article belongs to the Section Marine Pharmacology)
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15 pages, 1736 KiB  
Article
Structural Insights into the Marine Alkaloid Discorhabdin G as a Scaffold towards New Acetylcholinesterase Inhibitors
by Andrea Defant, Giacomo Carloni, Nicole Innocenti, Tomaž Trobec, Robert Frangež, Kristina Sepčić and Ines Mancini
Mar. Drugs 2024, 22(4), 173; https://doi.org/10.3390/md22040173 - 12 Apr 2024
Viewed by 851
Abstract
In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and [...] Read more.
In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis. The candidate molecule showed a slightly lower inhibitory potential against eeAChE but better inhibitory activity against hAChE than discorhabdin G, with a higher selectivity for AChEs than for BChE. It acted as a reversible competitive inhibitor, as previously observed for the natural alkaloid. The findings from the in vitro assay were relatively consistent with the data available from the AutoDock Vina and Protein-Ligand ANTSystem (PLANTS) calculations. Full article
(This article belongs to the Special Issue Marine Drug Discovery through Molecular Docking)
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15 pages, 4793 KiB  
Article
Equinins as Novel Broad-Spectrum Antimicrobial Peptides Isolated from the Cnidarian Actinia equina (Linnaeus, 1758)
by Claudia La Corte, Valentina Catania, Mariano Dara, Daniela Parrinello, Mariele Staropoli, Maria Rosa Trapani, Matteo Cammarata and Maria Giovanna Parisi
Mar. Drugs 2024, 22(4), 172; https://doi.org/10.3390/md22040172 - 12 Apr 2024
Viewed by 1345
Abstract
Sea anemones are valuable for therapeutic research as a diversified source of bioactive molecules, due to their diverse bioactive molecules linked to predation and defence mechanisms involving toxins and antimicrobial peptides. Acid extracts from Actinia equina tentacles and body were examined for antibacterial [...] Read more.
Sea anemones are valuable for therapeutic research as a diversified source of bioactive molecules, due to their diverse bioactive molecules linked to predation and defence mechanisms involving toxins and antimicrobial peptides. Acid extracts from Actinia equina tentacles and body were examined for antibacterial activity against Gram-positive, Gram-negative bacteria, and fungi. The peptide fractions showed interesting minimum inhibitory concentration (MIC) values (up to 0.125 µg/mL) against the tested pathogens. Further investigation and characterization of tentacle acid extracts with significant antimicrobial activity led to the purification of peptides through reverse phase chromatography on solid phase and HPLC. Broad-spectrum antimicrobial peptide activity was found in 40% acetonitrile fractions. The resulting peptides had a molecular mass of 2612.91 and 3934.827 Da and MIC ranging from 0.06 to 0.20 mg/mL. Sequencing revealed similarities to AMPs found in amphibians, fish, and Cnidaria, with anti-Gram+, Gram-, antifungal, candidacidal, anti-methicillin-resistant Staphylococcus aureus, carbapenemase-producing, vancomycin-resistant bacteria, and multi-drug resistant activity. Peptides 6.2 and 7.3, named Equinin A and B, respectively, were synthesized and evaluated in vitro towards the above-mentioned bacterial pathogens. Equinin B exerted interesting antibacterial activity (MIC and bactericidal concentrations of 1 mg/mL and 0.25 mg/mL, respectively) and gene organization supporting its potential in applied research. Full article
(This article belongs to the Section Marine Pharmacology)
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9 pages, 1224 KiB  
Article
Aurantoside L, a New Tetramic Acid Glycoside with Anti-Leishmanial Activity Isolated from the Marine Sponge Siliquariaspongia japonica
by Yasumoto Oyadomari, Yasuyuki Goto, Keisuke Suganuma, Shin-ichiro Kawazu, Leontine E. Becking, Nobuhiro Fusetani and Yoichi Nakao
Mar. Drugs 2024, 22(4), 171; https://doi.org/10.3390/md22040171 - 12 Apr 2024
Viewed by 874
Abstract
A new tetramic acid glycoside, aurantoside L (1), was isolated from the sponge Siliquariaspongia japonica collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L (1) composed of a tetramic acid bearing a chlorinated polyene system and [...] Read more.
A new tetramic acid glycoside, aurantoside L (1), was isolated from the sponge Siliquariaspongia japonica collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L (1) composed of a tetramic acid bearing a chlorinated polyene system and a trisaccharide part was elucidated using spectral analysis. Aurantoside L (1) showed anti-parasitic activity against L. amazonensis with an IC50 value of 0.74 µM. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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13 pages, 9005 KiB  
Article
Porphyran Attenuates Neuronal Loss in the Hippocampal CA1 Subregion Induced by Ischemia and Reperfusion in Gerbils by Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation
by Dae Won Kim, Tae-Kyeong Lee, Ji Hyeon Ahn, Se-Ran Yang, Myoung Cheol Shin, Jun Hwi Cho, Moo-Ho Won, Il Jun Kang and Joon Ha Park
Mar. Drugs 2024, 22(4), 170; https://doi.org/10.3390/md22040170 - 11 Apr 2024
Viewed by 809
Abstract
Porphyran, a sulfated polysaccharide found in various species of marine red algae, has been demonstrated to exhibit diverse bioactivities, including anti-inflammatory effects. However, the protective effects of porphyran against cerebral ischemia and reperfusion (IR) injury have not been investigated. The aim of this [...] Read more.
Porphyran, a sulfated polysaccharide found in various species of marine red algae, has been demonstrated to exhibit diverse bioactivities, including anti-inflammatory effects. However, the protective effects of porphyran against cerebral ischemia and reperfusion (IR) injury have not been investigated. The aim of this study was to examine the neuroprotective effects of porphyran against brain IR injury and its underlying mechanisms using a gerbil model of transient forebrain ischemia (IR in the forebrain), which results in pyramidal cell (principal neuron) loss in the cornu ammonis 1 (CA1) subregion of the hippocampus on day 4 after IR. Porphyran (25 and 50 mg/kg) was orally administered daily for one week prior to IR. Pretreatment with 50 mg/kg of porphyran, but not 25 mg/kg, significantly attenuated locomotor hyperactivity and protected pyramidal cells located in the CA1 area from IR injury. The pretreatment with 50 mg/kg of porphyran significantly suppressed the IR-induced activation and proliferation of microglia in the CA1 subregion. Additionally, the pretreatment significantly inhibited the overexpressions of nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing protein-3 (NLRP3) inflammasome complex, and pro-inflammatory cytokines (interleukin 1 beta and interleukin 18) induced by IR in the CA1 subregion. Overall, our findings suggest that porphyran exerts neuroprotective effects against brain IR injury, potentially by reducing the reaction (activation) and proliferation of microglia and reducing NLRP3 inflammasome-mediated neuroinflammation. Full article
(This article belongs to the Special Issue Marine Bioactive Compounds with Neuroprotective Potential)
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14 pages, 1545 KiB  
Article
Utilization of Lumpfish (Cyclopterus lumpus) Skin as a Source for Gelatine Extraction Using Acid Hydrolysis
by Abhilash Sasidharan, Elise Rabben Tronstad and Turid Rustad
Mar. Drugs 2024, 22(4), 169; https://doi.org/10.3390/md22040169 - 10 Apr 2024
Viewed by 1371
Abstract
Lumpfish (Cyclopterus lumpus) is an underutilized marine resource that is currently only being exploited for roe. Lumpfish skin was pre-treated with alkali (0.1M NaOH) and acid (0.1M HCl) at a skin to chemical ratio of 1:10 for 24 h at 5 [...] Read more.
Lumpfish (Cyclopterus lumpus) is an underutilized marine resource that is currently only being exploited for roe. Lumpfish skin was pre-treated with alkali (0.1M NaOH) and acid (0.1M HCl) at a skin to chemical ratio of 1:10 for 24 h at 5 °C to remove non-collagenous proteins and minerals. The pre-treated skin was washed, and gelatine was extracted with 0.1M of acetic acid at three different ratios (1:5, 1:10, and 1:15), time (12,18, and 24 h), and temperature combinations (12, 28, and 24 °C). The highest total extraction yield (>40%) was obtained with combinations of extraction ratios of 1:15 and 1:10 with a longer time (24 h) and higher temperature (18–24 °C). The highest gelatine content was obtained with an extraction period of 24 h and ratio of 1:10 (>80%). SDS-PAGE analysis confirmed the presence of type-I collagen. A rheological evaluation indicated melting and gelling temperatures, gel strength, and viscosity properties comparable to existing cold-water gelatine sources. Full article
(This article belongs to the Special Issue Fishery Discards, Processing Waste and Marine By-Products)
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22 pages, 1629 KiB  
Review
Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives
by João Cotas, Silvia Lomartire, Leonel Pereira, Ana Valado, João Carlos Marques and Ana M. M. Gonçalves
Mar. Drugs 2024, 22(4), 168; https://doi.org/10.3390/md22040168 - 10 Apr 2024
Viewed by 1745
Abstract
Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and [...] Read more.
Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness. Full article
(This article belongs to the Special Issue Perspectives for the Development of New Multitarget Marine Drugs)
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12 pages, 1167 KiB  
Review
Bacterioruberin: Biosynthesis, Antioxidant Activity, and Therapeutic Applications in Cancer and Immune Pathologies
by Micaela Giani, Carmen Pire and Rosa María Martínez-Espinosa
Mar. Drugs 2024, 22(4), 167; https://doi.org/10.3390/md22040167 - 9 Apr 2024
Viewed by 1066
Abstract
Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and [...] Read more.
Halophilic archaea, also termed haloarchaea, are a group of moderate and extreme halophilic microorganisms that constitute the major microbial populations in hypersaline environments. In these ecosystems, mainly aquatic, haloarchaea are constantly exposed to ionic and oxidative stress due to saturated salt concentrations and high incidences of UV radiation (mainly in summer). To survive under these harsh conditions, haloarchaea have developed molecular adaptations including hyperpigmentation. Regarding pigmentation, haloarchaeal species mainly synthesise the rare C50 carotenoid called bacterioruberin (BR) and its derivatives, monoanhydrobacterioruberin and bisanhydrobacterioruberin. Due to their colours and extraordinary antioxidant properties, BR and its derivatives have been the aim of research in several research groups all over the world during the last decade. This review aims to summarise the most relevant characteristics of BR and its derivatives as well as describe their reported antitumoral, immunomodulatory, and antioxidant biological activities. Based on their biological activities, these carotenoids can be considered promising natural biomolecules that could be used as tools to design new strategies and/or pharmaceutical formulas to fight against cancer, promote immunomodulation, or preserve skin health, among other potential uses. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents 3.0)
14 pages, 1364 KiB  
Article
Dehydration, Rehydration and Thermal Treatment: Effect on Bioactive Compounds of Red Seaweeds Porphyra umbilicalis and Porphyra linearis
by Carla Pires, Maria Sapatinha, Rogério Mendes, Narcisa M. Bandarra and Amparo Gonçalves
Mar. Drugs 2024, 22(4), 166; https://doi.org/10.3390/md22040166 - 9 Apr 2024
Viewed by 914
Abstract
The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the [...] Read more.
The nutritional and bioactive value of seaweeds is widely recognized, making them a valuable food source. To use seaweeds as food, drying and thermal treatments are required, but these treatments may have a negative impact on valuable bioactive compounds. In this study, the effects of dehydration, rehydration, and thermal treatment on the bioactive compounds (carotenoids, phycobiliproteins, total phenolic content (TPC), total flavonoids content (TFC)), antioxidant (ABTS and DPPH radical scavenging activities) and anti-Alzheimer’s (Acetylcholinesterase (AchE) inhibitory activities, and color properties of Porphyra umbilicalis and Porphyra linearis seaweeds were evaluated. The results revealed significant reductions in carotenoids, TPC, TFC, and antioxidant activities after the seaweeds’ processing, with differences observed between species. Thermal treatment led to the most pronounced reductions in bioactive compound contents and antioxidant activity. AchE inhibitory activity remained relatively high in all samples, with P. umbilicalis showing higher activity than P. linearis. Changes in color (ΔE) were significant after seaweeds’ dehydration, rehydration and thermal treatment, especially in P. umbilicalis. Overall, optimizing processing methods is crucial for preserving the bioactive compounds and biological activities of seaweeds, thus maximizing their potential as sustainable and nutritious food sources or as nutraceutical ingredients. Full article
(This article belongs to the Special Issue Fishery Discards, Processing Waste and Marine By-Products)
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24 pages, 1549 KiB  
Article
Synthesis and Late-Stage Modification of (−)-Doliculide Derivatives Using Matteson’s Homologation Approach
by Markus Tost and Uli Kazmaier
Mar. Drugs 2024, 22(4), 165; https://doi.org/10.3390/md22040165 - 8 Apr 2024
Viewed by 881
Abstract
(−)-Doliculide, a marine cyclodepsipeptide derived from the Japanese sea hare, Dolabella auricularia, exhibits potent cytotoxic properties, sparking interest in the field of synthetic chemistry. It is comprised of a peptide segment and a polyketide moiety, rendering it amenable to Matteson’s homologation methodology. [...] Read more.
(−)-Doliculide, a marine cyclodepsipeptide derived from the Japanese sea hare, Dolabella auricularia, exhibits potent cytotoxic properties, sparking interest in the field of synthetic chemistry. It is comprised of a peptide segment and a polyketide moiety, rendering it amenable to Matteson’s homologation methodology. This technique facilitates the diversification of the distinctive polyketide side chain, thereby permitting the introduction of functional groups in late stages for modifications of the derived compounds and studies on structure–activity relationships. Full article
(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application 2.0)
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23 pages, 9770 KiB  
Article
Tunable Oxidized-Chitin Hydrogels with Customizable Mechanical Properties by Metal or Hydrogen Ion Exposure
by Angelica Mucaria, Demetra Giuri, Claudia Tomasini, Giuseppe Falini and Devis Montroni
Mar. Drugs 2024, 22(4), 164; https://doi.org/10.3390/md22040164 - 3 Apr 2024
Viewed by 1022
Abstract
This study focuses on the optimization of chitin oxidation in C6 to carboxylic acid and its use to obtain a hydrogel with tunable resistance. After the optimization, water-soluble crystalline β-chitin fibrils (β-chitOx) with a degree of functionalization of 10% were obtained. Diverse reaction [...] Read more.
This study focuses on the optimization of chitin oxidation in C6 to carboxylic acid and its use to obtain a hydrogel with tunable resistance. After the optimization, water-soluble crystalline β-chitin fibrils (β-chitOx) with a degree of functionalization of 10% were obtained. Diverse reaction conditions were also tested for α-chitin, which showed a lower reactivity and a slower reaction kinetic. After that, a set of hydrogels was synthesized from β-chitOx 1 wt.% at pH 9, inducing the gelation by sonication. These hydrogels were exposed to different environments, such as different amounts of Ca2+, Na+ or Mg2+ solutions, buffered environments such as pH 9, PBS, pH 5, and pH 1, and pure water. These hydrogels were characterized using rheology, XRPD, SEM, and FT-IR. The notable feature of these hydrogels is their ability to be strengthened through cation chelation, being metal cations or hydrogen ions, with a five- to tenfold increase in their storage modulus (G’). The ions were theorized to alter the hydrogen-bonding network of the polymer and intercalate in chitin’s crystal structure along the a-axis. On the other hand, the hydrogel dissolved at pH 9 and pure water. These bio-based tunable hydrogels represent an intriguing material suitable for biomedical applications. Full article
(This article belongs to the Special Issue Application of Marine Chitin and Chitosan, 3rd Edition)
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21 pages, 4588 KiB  
Article
Sea Urchin Food Waste into Bioactives: Collagen and Polyhydroxynaphtoquinones from P. lividus and S. granularis
by Margherita Roncoroni, Giordana Martinelli, Stefano Farris, Stefania Marzorati and Michela Sugni
Mar. Drugs 2024, 22(4), 163; https://doi.org/10.3390/md22040163 - 3 Apr 2024
Viewed by 1014
Abstract
Approximately 75,000 tons of different sea urchin species are globally harvested for their edible gonads. Applying a circular economy approach, we have recently demonstrated that non-edible parts of the Mediterranean Sea urchin Paracentrotus lividus can be fully valorized into high-value products: antioxidant pigments [...] Read more.
Approximately 75,000 tons of different sea urchin species are globally harvested for their edible gonads. Applying a circular economy approach, we have recently demonstrated that non-edible parts of the Mediterranean Sea urchin Paracentrotus lividus can be fully valorized into high-value products: antioxidant pigments (polyhydroxynaphthoquinones—PHNQs) and fibrillar collagen can be extracted to produce innovative biomaterials for biomedical applications. Can waste from other edible sea urchin species (e.g., Sphaerechinus granularis) be similarly valorised? A comparative study on PHNQs and collagen extraction was conducted. PHNQ extraction yields were compared, pigments were quantified and identified, and antioxidant activities were assessed (by ABTS assay) and correlated to specific PHNQ presence (i.e., spinochrome E). Similarly, collagen extraction yields were evaluated, and the resulting collagen-based biomaterials were compared in terms of their ultrastructure, degradation kinetics, and resistance to compression. Results showed a partially similar PHNQ profile in both species, with significantly higher yield in P. lividus, while S. granularis exhibited better antioxidant activity. P. lividus samples showed higher collagen extraction yield, but S. granularis scaffolds showed higher stability. In conclusion, waste from different species can be successfully valorised through PHNQ and collagen extraction, offering diverse applications in the biomedical field, according to specific technical requirements. Full article
(This article belongs to the Special Issue Collagen and Bioactives from Marine By-Products)
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11 pages, 681 KiB  
Article
Content and Bioaccessibility of Minerals and Proteins in Fish-Bone Containing Side-Streams from Seafood Industries
by Marie Bagge Jensen, Jette Jakobsen, Charlotte Jacobsen, Jens J. Sloth, Jone Ibarruri, Carlos Bald, Bruno Iñarra, Niels Bøknæs and Ann-Dorit Moltke Sørensen
Mar. Drugs 2024, 22(4), 162; https://doi.org/10.3390/md22040162 - 3 Apr 2024
Viewed by 977
Abstract
With the aim to upcycle fish side-streams, enzymatic hydrolysis is often applied to produce protein hydrolysates with bioactive properties or just as a protein source for food and feed. However, the production of hydrolysates generates a side-stream. For underutilized fish and fish backbone [...] Read more.
With the aim to upcycle fish side-streams, enzymatic hydrolysis is often applied to produce protein hydrolysates with bioactive properties or just as a protein source for food and feed. However, the production of hydrolysates generates a side-stream. For underutilized fish and fish backbone this side-stream will contain fish bones and make it rich in minerals. The aim of this study was to assess the relative bioaccessibility (using the standardized in vitro model INFOGEST 2.0) of minerals in a dietary supplement compared to bone powder generated after enzymatic hydrolysis of three different fish side-streams: undersized whole hake, cod and salmon backbones consisting of insoluble protein and bones. Differences in the bioaccessibility of protein between the powders were also investigated. The enzyme hydrolysis was carried out using different enzymes and hydrolysis conditions for the different fish side-streams. The content and bioaccessibility of protein and the minerals phosphorus (P), calcium (Ca), potassium (K) and magnesium (Mg) were measured to evaluate the potential of the powder as an ingredient in, e.g., dietary supplements. The bone powders contained bioaccessible proteins and minerals. Thus, new side-streams generated from enzymatic hydrolysis can have possible applications in the food sector due to bioaccessible proteins and minerals. Full article
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14 pages, 3063 KiB  
Article
An Investigation of Quorum Sensing Inhibitors against Bacillus cereus in The Endophytic Fungus Pithomyces sacchari of the Laurencia sp.
by Shi-Liang Xiang, Kai-Zhong Xu, Lu-Jun Yin and Ai-Qun Jia
Mar. Drugs 2024, 22(4), 161; https://doi.org/10.3390/md22040161 - 31 Mar 2024
Viewed by 1267
Abstract
Bacillus cereus, a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A3, zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari [...] Read more.
Bacillus cereus, a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A3, zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari of the Laurencia sp. in the South China Sea. Among them, demethylincisterol A3, a sterol derivative, exhibited strong QS inhibitory activity against B. cereus. The QS inhibitory activity of demethylincisterol A3 was evaluated through experiments. The minimum inhibitory concentration (MIC) of demethylincisterol A3 against B. cereus was 6.25 μg/mL. At sub-MIC concentrations, it significantly decreased biofilm formation, hindered mobility, and diminished the production of protease and hemolysin activity. Moreover, RT-qPCR results demonstrated that demethylincisterol A3 markedly inhibited the expression of QS-related genes (plcR and papR) in B. cereus. The exposure to demethylincisterol A3 resulted in the downregulation of genes (comER, tasA, rpoN, sinR, codY, nheA, hblD, and cytK) associated with biofilm formation, mobility, and virulence factors. Hence, demethylincisterol A3 is a potentially effective compound in the pipeline of innovative antimicrobial therapies. Full article
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12 pages, 3623 KiB  
Article
Porous Nano-Fiber Structure of Modified Electrospun Chitosan GBR Membranes Improve Osteoblast Calcium Phosphate Deposition in Osteoblast-Fibroblast Co-Cultures
by Hengjie Su, Tomoko Fujiwara, Omar Skalli, Gretchen Schreyack Selders, Ting Li, Linna Mao and Joel D. Bumgardner
Mar. Drugs 2024, 22(4), 160; https://doi.org/10.3390/md22040160 - 30 Mar 2024
Viewed by 1095
Abstract
Desirable characteristics of electrospun chitosan membranes (ESCM) for guided bone regeneration are their nanofiber structure that mimics the extracellular fiber matrix and porosity for the exchange of signals between bone and soft tissue compartments. However, ESCM are susceptible to swelling and loss of [...] Read more.
Desirable characteristics of electrospun chitosan membranes (ESCM) for guided bone regeneration are their nanofiber structure that mimics the extracellular fiber matrix and porosity for the exchange of signals between bone and soft tissue compartments. However, ESCM are susceptible to swelling and loss of nanofiber and porous structure in physiological environments. A novel post-electrospinning method using di-tert-butyl dicarbonate (tBOC) prevents swelling and loss of nanofibrous structure better than sodium carbonate treatments. This study aimed to evaluate the hypothesis that retention of nanofiber morphology and high porosity of tBOC-modified ESCM (tBOC-ESCM) would support more bone mineralization in osteoblast-fibroblast co-cultures compared to Na2CO3 treated membranes (Na2CO3-ESCM) and solution-cast chitosan solid films (CM-film). The results showed that only the tBOC-ESCM retained the nanofibrous structure and had approximately 14 times more pore volume than Na2CO3-ESCM and thousands of times more pore volume than CM-films, respectively. In co-cultures, the tBOC-ESCM resulted in a significantly greater calcium-phosphate deposition by osteoblasts than either the Na2CO3-ESCM or CM-film (p < 0.05). This work supports the study hypothesis that tBOC-ESCM with nanofiber structure and high porosity promotes the exchange of signals between osteoblasts and fibroblasts, leading to improved mineralization in vitro and thus potentially improved bone healing and regeneration in guided bone regeneration applications Full article
(This article belongs to the Special Issue Application of Marine Chitin and Chitosan, 3rd Edition)
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