Next Issue
Volume 21, July
Previous Issue
Volume 21, May
 
 

Mar. Drugs, Volume 21, Issue 6 (June 2023) – 51 articles

Cover Story (view full-size image): Carotenoids, health-promoting compounds used in diverse industries, require sustainable sources beyond agriculture. This review explores marine archaea, bacteria, algae, and yeast as eco-friendly carotenoid producers. These organisms provide diverse carotenoids, including novel carotenoids, and their use supports Europe's Green Deal. However, the lack of standards, clinical studies, and toxicity analysis hinder their wider adoption. In addition, the production of carotenoids from marine organisms is a more expensive process compared to chemical synthesis. Further research on processing, biosynthetic pathways, extraction methods, and safety evaluation is needed to enhance the productivity and affordability of marine organisms as carotenoid sources. View this paper
  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Reader to open them.
Order results
Result details
Section
Select all
Export citation of selected articles as:
23 pages, 5612 KiB  
Article
Analogs of 6-Bromohypaphorine with Increased Agonist Potency for α7 Nicotinic Receptor as Anti-Inflammatory Analgesic Agents
by Igor A. Ivanov, Andrei E. Siniavin, Victor A. Palikov, Dmitry A. Senko, Irina V. Shelukhina, Lyubov A. Epifanova, Lucy O. Ojomoko, Svetlana Y. Belukhina, Nikita A. Prokopev, Mariia A. Landau, Yulia A. Palikova, Vitaly A. Kazakov, Natalia A. Borozdina, Arina V. Bervinova, Igor A. Dyachenko, Igor E. Kasheverov, Victor I. Tsetlin and Denis S. Kudryavtsev
Mar. Drugs 2023, 21(6), 368; https://doi.org/10.3390/md21060368 - 20 Jun 2023
Viewed by 1344
Abstract
Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC50 of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs [...] Read more.
Hypaphorines, tryptophan derivatives, have anti-inflammatory activity, but their mechanism of action was largely unknown. Marine alkaloid L-6-bromohypaphorine with EC50 of 80 μM acts as an agonist of α7 nicotinic acetylcholine receptor (nAChR) involved in anti-inflammatory regulation. We designed the 6-substituted hypaphorine analogs with increased potency using virtual screening of their binding to the α7 nAChR molecular model. Fourteen designed analogs were synthesized and tested in vitro by calcium fluorescence assay on the α7 nAChR expressed in neuro 2a cells, methoxy ester of D-6-iodohypaphorine (6ID) showing the highest potency (EC50 610 nM), being almost inactive toward α9α10 nAChR. The macrophages cytometry revealed an anti-inflammatory activity, decreasing the expression of TLR4 and increasing CD86, similarly to the action of PNU282987, a selective α7 nAChR agonist. 6ID administration in doses 0.1 and 0.5 mg/kg decreased carrageenan-induced allodynia and hyperalgesia in rodents, in accord with its anti-inflammatory action. Methoxy ester of D-6-nitrohypaphorine demonstrated anti-oedemic and analgesic effects in arthritis rat model at i.p. doses 0.05–0.26 mg/kg. Tested compounds showed excellent tolerability with no acute in vivo toxicity in dosages up to 100 mg/kg i.p. Thus, combining molecular modelling and natural product-inspired drug design improved the desired activity of the chosen nAChR ligand. Full article
Show Figures

Figure 1

14 pages, 2602 KiB  
Article
Expanding the Utility of Bioinformatic Data for the Full Stereostructural Assignments of Marinolides A and B, 24- and 26-Membered Macrolactones Produced by a Chemically Exceptional Marine-Derived Bacterium
by Min Cheol Kim, Jaclyn M. Winter, Reiko Cullum, Alexander J. Smith and William Fenical
Mar. Drugs 2023, 21(6), 367; https://doi.org/10.3390/md21060367 - 20 Jun 2023
Viewed by 1334
Abstract
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult [...] Read more.
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb mld biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis. Full article
(This article belongs to the Special Issue 20 Years Commemorative Issue in Honor of Professor Paul J. Scheuer)
Show Figures

Graphical abstract

18 pages, 826 KiB  
Article
Sequential Extraction of Valuable Bio-Products from Snow Crab (Chionoecetes opilio) Processing Discards Using Eco-Friendly Methods
by Heather J. Burke and Francesca Kerton
Mar. Drugs 2023, 21(6), 366; https://doi.org/10.3390/md21060366 - 20 Jun 2023
Viewed by 1374
Abstract
Green extraction methods using a combination of mechanical, enzymatic, and green chemical treatments were evaluated for the sequential extraction of carotenoid pigments, protein, and chitin from crab processing discards. Key objectives included avoiding the use of hazardous chemical solvents, conducting as close to [...] Read more.
Green extraction methods using a combination of mechanical, enzymatic, and green chemical treatments were evaluated for the sequential extraction of carotenoid pigments, protein, and chitin from crab processing discards. Key objectives included avoiding the use of hazardous chemical solvents, conducting as close to a 100% green extraction as possible, and developing simple processes to facilitate implementation into processing plants without the need for complicated and expensive equipment. Three crab bio-products were obtained: pigmented vegetable oil, pigmented protein powder, and chitin. Carotenoid extractions were performed using vegetable oils (corn, canola, and sunflower oils), giving between 24.85% and 37.93% astaxanthin recovery. Citric acid was used to demineralize the remaining material and afforded a pigmented protein powder. Three different proteases were used to deproteinate and isolate chitin in yields between 17.06% and 19.15%. The chitin was still highly colored and therefore decolorization was attempted using hydrogen peroxide. Characterization studies were conducted on each of the crab bio-products isolated including powder X-ray diffraction analysis on the chitin (80.18% crystallinity index, CI, achieved using green methods). Overall, three valuable bio-products could be obtained but further research is needed to obtain pigment-free chitin in an environmentally friendly manner. Full article
(This article belongs to the Special Issue High-Value Compounds from Marine Unutilized Resources)
Show Figures

Figure 1

23 pages, 979 KiB  
Review
Extraction of Nannochloropsis Fatty Acids Using Different Green Technologies: The Current Path
by Sérgio Cruz Sousa, Ana Cristina Freitas, Ana Maria Gomes and Ana P. Carvalho
Mar. Drugs 2023, 21(6), 365; https://doi.org/10.3390/md21060365 - 19 Jun 2023
Cited by 1 | Viewed by 1433
Abstract
Nannochloropsis is a genus of microalgae widely recognized as potential sources of distinct lipids, particularly polyunsaturated fatty acids (PUFA). These may be obtained through extraction, which has conventionally been performed using hazardous organic solvents. To substitute such solvents with “greener” alternatives, several technologies [...] Read more.
Nannochloropsis is a genus of microalgae widely recognized as potential sources of distinct lipids, particularly polyunsaturated fatty acids (PUFA). These may be obtained through extraction, which has conventionally been performed using hazardous organic solvents. To substitute such solvents with “greener” alternatives, several technologies have been studied to increase their extraction potential. Distinct technologies utilize different principles to achieve such objective; while some aim at disrupting the cell walls of the microalgae, others target the extraction per se. While some methods have been utilized independently, several technologies have also been combined, which has proven to be an effective strategy. The current review focuses on the technologies explored in the last five years to extract or increase extraction yields of fatty acids from Nannochloropsis microalgae. Depending on the extraction efficacy of the different technologies, distinct types of lipids and/or fatty acids are obtained accordingly. Moreover, the extraction efficiency may vary depending on the Nannochloropsis species. Hence, a case-by-case assessment must be conducted in order to ascertain the most suited technology, or tailor a specific one, to be applied to recover a particular fatty acid (or fatty acid class), namely PUFA, including eicosapentaenoic acid. Full article
(This article belongs to the Special Issue Fatty Acids from Marine Organisms)
Show Figures

Figure 1

12 pages, 6093 KiB  
Article
Inhibition Effects and Mechanisms of Marine Polysaccharide PSSD against Herpes Simplex Virus Type 2
by Han Yan, Jie Wang, Jiayi Yang, Zhongqiu Xu, Chunxia Li, Cui Hao, Shixin Wang and Wei Wang
Mar. Drugs 2023, 21(6), 364; https://doi.org/10.3390/md21060364 - 18 Jun 2023
Cited by 1 | Viewed by 1243
Abstract
Genital herpes is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which can increase the risk of HIV transmission and is a major health problem in the world. Thus, it is of great significance to develop new [...] Read more.
Genital herpes is a common sexually transmitted disease mainly caused by herpes simplex virus type 2 (HSV-2), which can increase the risk of HIV transmission and is a major health problem in the world. Thus, it is of great significance to develop new anti-HSV-2 drugs with high efficiency and low toxicity. In this study, the anti-HSV-2 activities of PSSD, a marine sulfated polysaccharide, was deeply explored both in vitro and in vivo. The results showed that PSSD had marked anti-HSV-2 activities in vitro with low cytotoxicity. PSSD can directly interact with virus particles to inhibit the adsorption of virus to the cell surface. PSSD may also interact with virus surface glycoproteins to block virus-induced membrane fusion. Importantly, PSSD can significantly attenuate the symptoms of genital herpes and weight loss in mice after gel smear treatment, as well as reducing the titer of virus shedding in the reproductive tract of mice, superior to the effect of acyclovir. In summary, the marine polysaccharide PSSD possesses anti-HSV-2 effects both in vitro and in vivo, and has potential to be developed into a novel anti-genital herpes agent in the future. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
Show Figures

Figure 1

24 pages, 4885 KiB  
Article
Antibacterial Activities and Life Cycle Stages of Asparagopsis armata: Implications of the Metabolome and Microbiome
by Christelle Parchemin, Delphine Raviglione, Anouar Mejait, Pierre Sasal, Elisabeth Faliex, Camille Clerissi and Nathalie Tapissier-Bontemps
Mar. Drugs 2023, 21(6), 363; https://doi.org/10.3390/md21060363 - 17 Jun 2023
Viewed by 1693
Abstract
The red alga Asparagopsis armata is a species with a haplodiplophasic life cycle alternating between morphologically distinct stages. The species is known for its various biological activities linked to the production of halogenated compounds, which are described as having several roles for the [...] Read more.
The red alga Asparagopsis armata is a species with a haplodiplophasic life cycle alternating between morphologically distinct stages. The species is known for its various biological activities linked to the production of halogenated compounds, which are described as having several roles for the algae such as the control of epiphytic bacterial communities. Several studies have reported differences in targeted halogenated compounds (using gas chromatography–mass spectrometry analysis (GC-MS)) and antibacterial activities between the tetrasporophyte and the gametophyte stages. To enlarge this picture, we analysed the metabolome (using liquid chromatography–mass spectrometry (LC-MS)), the antibacterial activity and the bacterial communities associated with several stages of the life cycle of A. armata: gametophytes, tetrasporophytes and female gametophytes with developed cystocarps. Our results revealed that the relative abundance of several halogenated molecules including dibromoacetic acid and some more halogenated molecules fluctuated depending on the different stages of the algae. The antibacterial activity of the tetrasporophyte extract was significantly higher than that of the extracts of the other two stages. Several highly halogenated compounds, which discriminate algal stages, were identified as candidate molecules responsible for the observed variation in antibacterial activity. The tetrasporophyte also harboured a significantly higher specific bacterial diversity, which is associated with a different bacterial community composition than the other two stages. This study provides elements that could help in understanding the processes that take place throughout the life cycle of A. armata with different potential energy investments between the development of reproductive elements, the production of halogenated molecules and the dynamics of bacterial communities. Full article
(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)
Show Figures

Graphical abstract

16 pages, 3228 KiB  
Article
New Antibacterial Diterpenoids from the South China Sea Soft Coral Klyxum molle
by Jia-Dong Yu, Dan-Dan Yu, Ming-Zhi Su, Yu-Cheng Gu, Hong Wang and Yue-Wei Guo
Mar. Drugs 2023, 21(6), 362; https://doi.org/10.3390/md21060362 - 16 Jun 2023
Cited by 1 | Viewed by 1316
Abstract
Fifteen new diterpenoids, namely xishaklyanes A-O (115), along with three known related ones (1618), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds [...] Read more.
Fifteen new diterpenoids, namely xishaklyanes A-O (115), along with three known related ones (1618), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher’s method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 μg/mL against Lactococcus garvieae. Full article
Show Figures

Graphical abstract

11 pages, 1223 KiB  
Article
Sesquiterpenes from Streptomyces qinglanensis and Their Cytotoxic Activity
by Cao Van Anh, Jong Soon Kang, Jeong-Wook Yang, Joo-Hee Kwon, Chang-Su Heo, Hwa-Sun Lee, Chan Hong Park and Hee Jae Shin
Mar. Drugs 2023, 21(6), 361; https://doi.org/10.3390/md21060361 - 16 Jun 2023
Cited by 1 | Viewed by 1292
Abstract
Nine sesquiterpenes, including eight pentalenenes (18) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. [...] Read more.
Nine sesquiterpenes, including eight pentalenenes (18) and one bolinane derivative (9), were isolated from the culture broth of a marine-derived actinobacterium Streptomyces qinglanensis 213DD-006. Among them, 1, 4, 7, and 9 were new compounds. Their planar structures were determined by spectroscopic methods (HRMS, 1D, and 2D NMR), and the absolute configuration was established by biosynthesis consideration and electronic-circular-dichroism (ECD) calculations. All the isolated compounds were screened for their cytotoxicity against six solid and seven blood cancer cell lines. Compounds 46 and 8 showed a moderate activity against all of the tested solid cell lines, with GI50 values ranging from 1.97 to 3.46 µM. Full article
(This article belongs to the Special Issue Marine Drug Research in Korea II)
Show Figures

Graphical abstract

20 pages, 11090 KiB  
Article
Antioxidant Peptides from Monkfish Swim Bladders: Ameliorating NAFLD In Vitro by Suppressing Lipid Accumulation and Oxidative Stress via Regulating AMPK/Nrf2 Pathway
by Ming-Feng Wu, Qing-Hao Xi, Yan Sheng, Yu-Mei Wang, Wan-Yi Wang, Chang-Feng Chi and Bin Wang
Mar. Drugs 2023, 21(6), 360; https://doi.org/10.3390/md21060360 - 16 Jun 2023
Cited by 31 | Viewed by 1597
Abstract
In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the [...] Read more.
In this study, we investigate the ameliorating functions of QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) from monkfish swim bladders on an FFA-induced NAFLD model of HepG2 cells. The lipid-lowering mechanisms revealed that these five oligopeptides can up-regulate the expression of phospho-AMP-activated protein kinase (p-AMPK) proteins to inhibit the expression of the sterol regulatory element binding protein-1c (SREBP-1c) proteins on increasing lipid synthesis and up-regulating the expression of the PPAP-α and CPT-1 proteins on promoting the β-oxidation of fatty acids. Moreover, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) can significantly inhibit reactive oxygen species’ (ROS) production, promote the activities of intracellular antioxidases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; and catalase, CAT) and bring down the content of malondialdehyde (MDA) derived from lipid peroxidation. Further investigations revealed that the regulation of these five oligopeptides on oxidative stress was achieved through activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to raise the expression levels of the heme oxygenase 1 (HO-1) protein and downstream antioxidant proteases. Therefore, QDYD (MSP2), ARW (MSP8), DDGGK (MSP10), YPAGP (MSP13) and DPAGP (MSP18) could serve as candidate ingredients to develop functional products for treating NAFLD. Full article
Show Figures

Graphical abstract

68 pages, 7649 KiB  
Review
Cyanobacteria: A Promising Source of Antifungal Metabolites
by Samuel Cavalcante do Amaral, Luciana Pereira Xavier, Vítor Vasconcelos and Agenor Valadares Santos
Mar. Drugs 2023, 21(6), 359; https://doi.org/10.3390/md21060359 - 14 Jun 2023
Viewed by 4586
Abstract
Cyanobacteria are a rich source of secondary metabolites, and they have received a great deal of attention due to their applicability in different industrial sectors. Some of these substances are known for their notorious ability to inhibit fungal growth. Such metabolites are very [...] Read more.
Cyanobacteria are a rich source of secondary metabolites, and they have received a great deal of attention due to their applicability in different industrial sectors. Some of these substances are known for their notorious ability to inhibit fungal growth. Such metabolites are very chemically and biologically diverse. They can belong to different chemical classes, including peptides, fatty acids, alkaloids, polyketides, and macrolides. Moreover, they can also target different cell components. Filamentous cyanobacteria have been the main source of these compounds. This review aims to identify the key features of these antifungal agents, as well as the sources from which they are obtained, their major targets, and the environmental factors involved when they are being produced. For the preparation of this work, a total of 642 documents dating from 1980 to 2022 were consulted, including patents, original research, review articles, and theses. Full article
(This article belongs to the Section Marine Pharmacology)
Show Figures

Figure 1

16 pages, 2380 KiB  
Article
High Solubility and Bioavailability of Lobster Shell-Derived Calcium for Significantly Proliferating Bone and Skin Cells In Vitro
by Trung T. Nguyen, Thanh Hoang, Tuyet Pham, Vi Khanh Truong, Xuan Luo, Jian Qin and Wei Zhang
Mar. Drugs 2023, 21(6), 358; https://doi.org/10.3390/md21060358 - 11 Jun 2023
Viewed by 1672
Abstract
Shell wastes pose environmental and financial burdens to the shellfish industry. Utilizing these undervalued shells for commercial chitin production could minimize their adverse impacts while maximizing economic value. Shell chitin conventionally produced through harsh chemical processes is environmentally unfriendly and infeasible for recovering [...] Read more.
Shell wastes pose environmental and financial burdens to the shellfish industry. Utilizing these undervalued shells for commercial chitin production could minimize their adverse impacts while maximizing economic value. Shell chitin conventionally produced through harsh chemical processes is environmentally unfriendly and infeasible for recovering compatible proteins and minerals for value-added products. However, we recently developed a microwave-intensified biorefinery that efficiently produced chitin, proteins/peptides, and minerals from lobster shells. Lobster minerals have a calcium-rich composition and biologically originated calcium is more biofunctional for use as a functional, dietary, or nutraceutical ingredient in many commercial products. This has suggested a further investigation of lobster minerals for commercial applications. In this study, the nutritional attributes, functional properties, nutraceutical effects, and cytotoxicity of lobster minerals were analyzed using in vitro simulated gastrointestinal digestion combined with growing bone (MG-63), skin (HaCaT), and macrophage (THP-1) cells. The calcium from the lobster minerals was found to be comparable to that of a commercial calcium supplement (CCS, 139 vs. 148 mg/g). In addition, beef incorporated with lobster minerals (2%, w/w) retained water better than that of casein and commercial calcium lactate (CCL, 21.1 vs. 15.1 and 13.3%), and the lobster mineral had a considerably higher oil binding capacity than its rivals (casein and CCL, 2.5 vs. 1.5 and 1.0 mL/g). Notably, the lobster mineral and its calcium were far more soluble than the CCS (98.4 vs. 18.6% for the products and 64.0 vs. 8.5% for their calcium) while the in vitro bioavailability of lobster calcium was 5.9-fold higher compared to that of the commercial product (11.95 vs. 1.99%). Furthermore, supplementing lobster minerals in media at ratios of 15%, 25%, and 35% (v/v) when growing cells did not induce any detectable changes in cell morphology and apoptosis. However, it had significant effects on cell growth and proliferation. The responses of cells after three days of culture supplemented with the lobster minerals, compared to the CCS supplementation, were significantly better with the bone cells (MG-63) and competitively quick with the skin cells (HaCaT). The cell growth reached 49.9–61.6% for the MG-63 and 42.9–53.4% for the HaCaT. Furthermore, the MG-63 and HaCaT cells proliferated considerably after seven days of incubation, reaching 100.3% for MG-63 and 115.9% for HaCaT with a lobster mineral supplementation of 15%. Macrophages (THP-1 cells) treated for 24 h with lobster minerals at concentrations of 1.24–2.89 mg/mL had no detectable changes in cell morphology while their viability was over 82.2%, far above the cytotoxicity threshold (<70%). All these results indicate that lobster minerals could be used as a source of functional or nutraceutical calcium for commercial products. Full article
(This article belongs to the Special Issue High-Value Compounds from Marine Unutilized Resources)
Show Figures

Figure 1

17 pages, 3223 KiB  
Article
Isolation of Mycosporine-like Amino Acids from Red Macroalgae and a Marine Lichen by High-Performance Countercurrent Chromatography: A Strategy to Obtain Biological UV-Filters
by Julia Vega, Daniela Bárcenas-Pérez, David Fuentes-Ríos, Juan Manuel López-Romero, Pavel Hrouzek, Félix López Figueroa and José Cheel
Mar. Drugs 2023, 21(6), 357; https://doi.org/10.3390/md21060357 - 10 Jun 2023
Viewed by 1353
Abstract
Marine organisms have gained considerable biotechnological interest in recent years due to their wide variety of bioactive compounds with potential applications. Mycosporine-like amino acids (MAAs) are UV-absorbing secondary metabolites with antioxidant and photoprotective capacity, mainly found in organisms living under stress conditions (e.g., [...] Read more.
Marine organisms have gained considerable biotechnological interest in recent years due to their wide variety of bioactive compounds with potential applications. Mycosporine-like amino acids (MAAs) are UV-absorbing secondary metabolites with antioxidant and photoprotective capacity, mainly found in organisms living under stress conditions (e.g., cyanobacteria, red algae, or lichens). In this work, five MAAs were isolated from two red macroalgae (Pyropia columbina and Gelidium corneum) and one marine lichen (Lichina pygmaea) by high-performance countercurrent chromatography (HPCCC). The selected biphasic solvent system consisted of ethanol, acetonitrile, saturated ammonium sulphate solution, and water (1:1:0.5:1; v:v:v:v). The HPCCC process for P. columbina and G. corneum consisted of eight separation cycles (1 g and 200 mg of extract per cycle, respectively), whereas three cycles were performed for of L. pygmaea (1.2 g extract per cycle). The separation process resulted in fractions enriched with palythine (2.3 mg), asterina-330 (3.3 mg), shinorine (14.8 mg), porphyra-334 (203.5 mg) and mycosporine-serinol (46.6 mg), which were subsequently desalted by using precipitation with methanol and permeation on a Sephadex G-10 column. Target molecules were identified by HPLC, MS, and NMR. Full article
(This article belongs to the Special Issue Marine Algal Biorefinery for Bioactive Compound Production)
Show Figures

Figure 1

12 pages, 1670 KiB  
Article
Synthesis and Biological Activity of Novel α-Conotoxins Derived from Endemic Polynesian Cone Snails
by Yazid Mohamed Souf, Gonxhe Lokaj, Veeresh Kuruva, Yakop Saed, Delphine Raviglione, Ashraf Brik, Annette Nicke, Nicolas Inguimbert and Sébastien Dutertre
Mar. Drugs 2023, 21(6), 356; https://doi.org/10.3390/md21060356 - 09 Jun 2023
Viewed by 1435
Abstract
α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, [...] Read more.
α-Conotoxins are well-known probes for the characterization of the various subtypes of nicotinic acetylcholine receptors (nAChRs). Identifying new α-conotoxins with different pharmacological profiles can provide further insights into the physiological or pathological roles of the numerous nAChR isoforms found at the neuromuscular junction, the central and peripheral nervous systems, and other cells such as immune cells. This study focuses on the synthesis and characterization of two novel α-conotoxins obtained from two species endemic to the Marquesas Islands, namely Conus gauguini and Conus adamsonii. Both species prey on fish, and their venom is considered a rich source of bioactive peptides that can target a wide range of pharmacological receptors in vertebrates. Here, we demonstrate the versatile use of a one-pot disulfide bond synthesis to achieve the α-conotoxin fold [Cys 1-3; 2-4] for GaIA and AdIA, using the 2-nitrobenzyl (NBzl) protecting group of cysteines for effective regioselective oxidation. The potency and selectivity of GaIA and AdIA against rat nicotinic acetylcholine receptors were investigated electrophysiologically and revealed potent inhibitory activities. GaIA was most active at the muscle nAChR (IC50 = 38 nM), whereas AdIA was most potent at the neuronal α6/3 β2β3 subtype (IC50 = 177 nM). Overall, this study contributes to a better understanding of the structure–activity relationships of α-conotoxins, which may help in the design of more selective tools. Full article
(This article belongs to the Special Issue Conotoxin and Conotoxin Analogues: A Pharmacy Cabinet under the Sea)
Show Figures

Figure 1

28 pages, 857 KiB  
Article
Variability in Macro- and Micronutrients of 15 Rarely Researched Microalgae
by Fabian Sandgruber, Annekathrin Gielsdorf, Benjamin Schenz, Sandra Marie Müller, Tanja Schwerdtle, Stefan Lorkowski, Carola Griehl and Christine Dawczynski
Mar. Drugs 2023, 21(6), 355; https://doi.org/10.3390/md21060355 - 09 Jun 2023
Cited by 1 | Viewed by 3373
Abstract
Microalgae have enormous potential for human nutrition, yet the European Commission has authorized the consumption of only eleven species. Strains of fifteen rarely researched microalgae from two kingdoms were screened regarding their nutritional profile and value for human health in two cultivation phases. [...] Read more.
Microalgae have enormous potential for human nutrition, yet the European Commission has authorized the consumption of only eleven species. Strains of fifteen rarely researched microalgae from two kingdoms were screened regarding their nutritional profile and value for human health in two cultivation phases. Contents of protein, fiber, lipids, fatty acids, minerals, trace elements and heavy metals were determined. In the growth phase, microalgae accumulated more arginine, histidine, ornithine, pure and crude protein, Mg, Mn, Fe and Zn and less Ni, Mo and I2 compared to the stationary phase. Higher contents of total fat, C14:0, C14:1n5, C16:1n7, C20:4n6, C20:5n3 and also As were observed in microalgae from the chromista kingdom in comparison to microalgae from the plantae kingdom (p < 0.05). Conversely, the latter had higher contents of C20:0, C20:1n9 and C18:3n3 as well as Ca and Pb (p < 0.05). More precisely, Chrysotila carterae appeared to have great potential for human nutrition because of its high nutrient contents such as fibers, carotenoids, C20:6n3, Mg, Ca, Mn, Fe, Se, Zn, Ni, Mo and I2. In summary, microalgae may contribute to a large variety of nutrients, yet the contents differ between kingdoms, cultivation phases and also species. Full article
(This article belongs to the Special Issue Metabolites in Marine Planktonic Organisms)
Show Figures

Graphical abstract

18 pages, 3628 KiB  
Article
Supplementation of n-3 PUFAs in Adulthood Attenuated Susceptibility to Pentylenetetrazol Induced Epilepsy in Mice Fed with n-3 PUFAs Deficient Diet in Early Life
by Ying-Cai Zhao, Cheng-Cheng Wang, Xiao-Yue Li, Dan-Dan Wang, Yu-Ming Wang, Chang-Hu Xue, Min Wen and Tian-Tian Zhang
Mar. Drugs 2023, 21(6), 354; https://doi.org/10.3390/md21060354 - 09 Jun 2023
Viewed by 1289
Abstract
The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the [...] Read more.
The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice’s offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure. Full article
Show Figures

Graphical abstract

26 pages, 4323 KiB  
Review
State of Innovation in Alginate-Based Materials
by Katarzyna Adamiak and Alina Sionkowska
Mar. Drugs 2023, 21(6), 353; https://doi.org/10.3390/md21060353 - 08 Jun 2023
Cited by 2 | Viewed by 3144
Abstract
This review article presents past and current alginate-based materials in each application, showing the widest range of alginate’s usage and development in the past and in recent years. The first segment emphasizes the unique characteristics of alginates and their origin. The second segment [...] Read more.
This review article presents past and current alginate-based materials in each application, showing the widest range of alginate’s usage and development in the past and in recent years. The first segment emphasizes the unique characteristics of alginates and their origin. The second segment sets alginates according to their application based on their features and limitations. Alginate is a polysaccharide and generally occurs as water-soluble sodium alginate. It constitutes hydrophilic and anionic polysaccharides originally extracted from natural brown algae and bacteria. Due to its promising properties, such as gelling, moisture retention, and film-forming, it can be used in environmental protection, cosmetics, medicine, tissue engineering, and the food industry. The comparison of publications with alginate-based products in the field of environmental protection, medicine, food, and cosmetics in scientific articles showed that the greatest number was assigned to the environmental field (30,767) and medicine (24,279), whereas fewer publications were available in cosmetic (5692) and food industries (24,334). Data are provided from the Google Scholar database (including abstract, title, and keywords), accessed in May 2023. In this review, various materials based on alginate are described, showing detailed information on modified composites and their possible usage. Alginate’s application in water remediation and its significant value are highlighted. In this study, existing knowledge is compared, and this paper concludes with its future prospects. Full article
Show Figures

Figure 1

18 pages, 1342 KiB  
Review
Nanoparticles from Microalgae and Their Biomedical Applications
by Agnieszka Sidorowicz, Giacomo Fais, Mattia Casula, Massimiliano Borselli, Giuseppe Giannaccare, Antonio Mario Locci, Nicola Lai, Roberto Orrù, Giacomo Cao and Alessandro Concas
Mar. Drugs 2023, 21(6), 352; https://doi.org/10.3390/md21060352 - 07 Jun 2023
Cited by 8 | Viewed by 2143
Abstract
Over the years, microalgae have been a source of useful compounds mainly used as food and dietary supplements. Recently, microalgae have been used as a source of metabolites that can participate in the synthesis of several nanoparticles through inexpensive and environmentally friendly routes [...] Read more.
Over the years, microalgae have been a source of useful compounds mainly used as food and dietary supplements. Recently, microalgae have been used as a source of metabolites that can participate in the synthesis of several nanoparticles through inexpensive and environmentally friendly routes alternative to chemical synthesis. Notably, the occurrence of global health threats focused attention on the microalgae application in the medicinal field. In this review, we report the influence of secondary metabolites from marine and freshwater microalgae and cyanobacteria on the synthesis of nanoparticles that were applied as therapeutics. In addition, the use of isolated compounds on the surface of nanoparticles to combat diseases has also been addressed. Although studies have proven the beneficial effect of high-value bioproducts on microalgae and their potential in medicine, there is still room for understanding their exact role in the human body and translating lab-based research into clinical trials. Full article
(This article belongs to the Special Issue Nanoparticles Synthesis with Marine Substances)
Show Figures

Figure 1

20 pages, 1399 KiB  
Article
1-O-alkyl-glycerols from Squid Berryteuthis magister Reduce Inflammation and Modify Fatty Acid and Plasmalogen Metabolism in Asthma Associated with Obesity
by Yulia Denisenko, Tatyana Novgorodtseva, Marina Antonyuk, Alla Yurenko, Tatyana Gvozdenko, Sergey Kasyanov, Ekaterina Ermolenko and Ruslan Sultanov
Mar. Drugs 2023, 21(6), 351; https://doi.org/10.3390/md21060351 - 07 Jun 2023
Viewed by 1333
Abstract
Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed [...] Read more.
Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed to investigate the effect of AGs from squid Berryteuthis magister on lung function, fatty acid and plasmalogen levels, and cytokine and adipokine production in obese patients with asthma. The investigational trial included 19 patients with mild asthma associated with obesity who received 0.4 g of AGs daily for three months in addition to their standard treatment. The effects of AGs were evaluated at one and three months of treatment. The results of the study demonstrated that intake of AGs increased the FEV1 and FEV1/VC ratios, and significantly decreased the ACQ score in 17 of the 19 patients after three months of treatment. The intake of AGs increased concentration of plasmalogen and n–3 PUFA in plasma, and modified leptin/adiponectin production by adipose tissue. The supplementation of AGs decreased the plasma levels of inflammatory cytokines (TNF-α, IL-4, and IL-17a), and oxylipins (TXB2 and LTB4), suggesting an anti-inflammatory property of AGs. In conclusion, 1-O-alkyl-glycerols could be a promising dietary supplement for improving pulmonary function and reducing inflammation in obese asthma patients, and a natural source for plasmalogen synthesis. The study highlighted that the beneficial effects of AG consumption can be observed after one month of treatment, with gradual improvement after three months of supplementation. Full article
(This article belongs to the Special Issue Marine Drugs Research in Russia)
Show Figures

Figure 1

26 pages, 1891 KiB  
Review
Fish Skin Mucus Extracts: An Underexplored Source of Antimicrobial Agents
by Rocío Díaz-Puertas, Mikolaj Adamek, Ricardo Mallavia and Alberto Falco
Mar. Drugs 2023, 21(6), 350; https://doi.org/10.3390/md21060350 - 07 Jun 2023
Cited by 4 | Viewed by 6262
Abstract
The slow discovery of new antibiotics combined with the alarming emergence of antibiotic-resistant bacteria underscores the need for alternative treatments. In this regard, fish skin mucus has been demonstrated to contain a diverse array of bioactive molecules with antimicrobial properties, including peptides, proteins, [...] Read more.
The slow discovery of new antibiotics combined with the alarming emergence of antibiotic-resistant bacteria underscores the need for alternative treatments. In this regard, fish skin mucus has been demonstrated to contain a diverse array of bioactive molecules with antimicrobial properties, including peptides, proteins, and other metabolites. This review aims to provide an overview of the antimicrobial molecules found in fish skin mucus and its reported in vitro antimicrobial capacity against bacteria, fungi, and viruses. Additionally, the different methods of mucus extraction, which can be grouped as aqueous, organic, and acidic extractions, are presented. Finally, omic techniques (genomics, transcriptomics, proteomics, metabolomics, and multiomics) are described as key tools for the identification and isolation of new antimicrobial compounds. Overall, this study provides valuable insight into the potential of fish skin mucus as a promising source for the discovery of new antimicrobial agents. Full article
(This article belongs to the Special Issue Fishery Discards, Processing Waste and Marine By-Products)
Show Figures

Figure 1

24 pages, 6903 KiB  
Article
Synthesis of Brominated Lactones Related to Mycalin A: Selective Antiproliferative Activity on Metastatic Melanoma Cells and Inhibition of the Cell Migration
by Domenica Capasso, Paola Marino, Sonia Di Gaetano, Nicola Borbone, Monica Terracciano, Roberta Trani, Caterina Longo and Vincenzo Piccialli
Mar. Drugs 2023, 21(6), 349; https://doi.org/10.3390/md21060349 - 07 Jun 2023
Cited by 2 | Viewed by 1095
Abstract
Starting from D-xylonolactone and D-ribonolactone, several five-membered bromolactones, related to the C1–C5 portion of mycalin A lactone, have been synthesized. The bromination of D-ribonolactone with HBr/AcOH, without a subsequent transesterification step, has been studied for the first time, giving us most of the [...] Read more.
Starting from D-xylonolactone and D-ribonolactone, several five-membered bromolactones, related to the C1–C5 portion of mycalin A lactone, have been synthesized. The bromination of D-ribonolactone with HBr/AcOH, without a subsequent transesterification step, has been studied for the first time, giving us most of the acetylated lactones investigated in the present study. For each compound, where possible, both the C-3 alcohol and the corresponding acetate were prepared. Evaluation of their anti-tumor activity showed that all the acetates possess a good cytotoxicity towards human melanoma (A375), human cervical adenocarcinoma (HeLa) and human metastatic melanoma (WM266) cancer cells, comparable or even higher than that displayed by the original mycalin A lactone. Lactone acetates derived from D-ribonolactone showed the higher selectivity of action, exhibiting a strong cytotoxicity on all the tested tumor cells but only a limited toxicity on healthy human dermal fibroblast (HDF) cells, used as a control. Wound healing assays showed that two of these substances inhibit the migration of the WM266 cells. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
Show Figures

Graphical abstract

16 pages, 2200 KiB  
Article
Anti-SARS-CoV-2 Activity of Polysaccharides Extracted from Halymenia floresii and Solieria chordalis (Rhodophyta)
by Clément Jousselin, Hugo Pliego-Cortés, Alexia Damour, Magali Garcia, Charles Bodet, Daniel Robledo, Nathalie Bourgougnon and Nicolas Lévêque
Mar. Drugs 2023, 21(6), 348; https://doi.org/10.3390/md21060348 - 06 Jun 2023
Cited by 2 | Viewed by 1811
Abstract
Even after hundreds of clinical trials, the search for new antivirals to treat COVID-19 is still relevant. Carrageenans are seaweed sulfated polysaccharides displaying antiviral activity against a wide range of respiratory viruses. The objective of this work was to study the antiviral properties [...] Read more.
Even after hundreds of clinical trials, the search for new antivirals to treat COVID-19 is still relevant. Carrageenans are seaweed sulfated polysaccharides displaying antiviral activity against a wide range of respiratory viruses. The objective of this work was to study the antiviral properties of Halymenia floresii and Solieria chordalis carrageenans against SARS-CoV-2. Six polysaccharide fractions obtained from H. floresii and S. chordalis by Enzyme-Assisted Extraction (EAE) or Hot Water Extraction (HWE) were tested. The effect of carrageenan on viral replication was assessed during infection of human airway epithelial cells with a clinical strain of SARS-CoV-2. The addition of carrageenans at different times of the infection helped to determine their mechanism of antiviral action. The four polysaccharide fractions isolated from H. floresii displayed antiviral properties while the S. chordalis fractions did not. EAE-purified fractions caused a stronger reduction in viral RNA concentration. Their antiviral action is likely related to an inhibition of the virus attachment to the cell surface. This study confirms that carrageenans could be used as first-line treatment in the respiratory mucosa to inhibit the infection and transmission of SARS-CoV-2. Low production costs, low cytotoxicity, and a broad spectrum of antiviral properties constitute the main strengths of these natural molecules. Full article
(This article belongs to the Special Issue Marine Natural Products against Coronaviruses)
Show Figures

Figure 1

16 pages, 2876 KiB  
Article
The Anti-Inflammatory Effect of Low Molecular Weight Fucoidan from Sargassum siliquastrum in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages via Inhibiting NF-κB/MAPK Signaling Pathways
by Arachchige Maheshika Kumari Jayasinghe, Kirinde Gedara Isuru Sandanuwan Kirindage, Ilekuttige Priyan Shanura Fernando, Kil-Nam Kim, Jae-Young Oh and Ginnae Ahn
Mar. Drugs 2023, 21(6), 347; https://doi.org/10.3390/md21060347 - 04 Jun 2023
Cited by 7 | Viewed by 1665
Abstract
Brown seaweed is a rich source of fucoidan, which exhibits a variety of biological activities. The present study discloses the protective effect of low molecular weight fucoidan (FSSQ) isolated from an edible brown alga, Sargassum siliquastrum, on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW [...] Read more.
Brown seaweed is a rich source of fucoidan, which exhibits a variety of biological activities. The present study discloses the protective effect of low molecular weight fucoidan (FSSQ) isolated from an edible brown alga, Sargassum siliquastrum, on lipopolysaccharide (LPS)-stimulated inflammatory responses in RAW 264.7 macrophages. The findings of the study revealed that FSSQ increases cell viability while decreasing intracellular reactive oxygen species production in LPS-stimulated RAW 264.7 macrophages dose-dependently. FSSQ reduced the iNOS and COX-2 expression, inhibiting the NO and prostaglandin E2 production. Furthermore, mRNA expression of IL-1β, IL-6, and TNF-α was downregulated by FSSQ via modulating MAPK and NF-κB signaling. The NLRP3 inflammasome protein complex, including NLRP3, ASC, and caspase-1, as well as the subsequent release of pro-inflammatory cytokines, such as IL-1β and IL-18, release in LPS-stimulated RAW 264.7 macrophages was inhibited by FSSQ. The cytoprotective effect of FSSQ is indicated via Nrf2/HO-1 signaling activation, which is considerably reduced upon suppression of HO-1 activity by ZnPP. Collectively, the study revealed the therapeutic potential of FSSQ against inflammatory responses in LPS-stimulated RAW 264.7 macrophages. Moreover, the study suggests further investigations on commercially viable methods for fucoidan isolation. Full article
(This article belongs to the Special Issue Fucoidans: Structures-Based Bioactivities)
Show Figures

Figure 1

12 pages, 2051 KiB  
Article
Comparing the Ability of Secretory Signal Peptides for Heterologous Expression of Anti-Lipopolysaccharide Factor 3 in Chlamydomonas reinhardtii
by Huilin Zhuang, Yaohui Ou, Ruoyu Chen, Danqiong Huang and Chaogang Wang
Mar. Drugs 2023, 21(6), 346; https://doi.org/10.3390/md21060346 - 04 Jun 2023
Viewed by 1223
Abstract
Anti-lipopolysaccharide factor 3 (ALFPm3) possesses a wide antimicrobial spectrum and high antibacterial and viral activities for broad application prospects in the aquaculture industry. However, the application of ALFPm3 is limited by its low production in nature, as well as [...] Read more.
Anti-lipopolysaccharide factor 3 (ALFPm3) possesses a wide antimicrobial spectrum and high antibacterial and viral activities for broad application prospects in the aquaculture industry. However, the application of ALFPm3 is limited by its low production in nature, as well as its low activity when expressed in Escherichia coli and yeast. Although it has been proven that its secretory expression can be used to produce antimicrobial peptides with strong antimicrobial activity, there is no study on the high-efficiency secretory expression of ALFPm3 in Chlamydomonas reinhardtii. In this study, signal peptides ARS1 and CAH1 were fused with ALFPm3 and inserted into the pESVH vector to construct pH-aALF and pH-cALF plasmids, respectively, that were transformed to C. reinhardtii JUV using the glass bead method. Subsequently, through antibiotic screening, DNA-PCR, and RT-PCR, transformants expressing ALFPm3 were confirmed and named T-JaA and T-JcA, respectively. The peptide ALFPm3 could be detected in algal cells and culture medium by immunoblot, meaning that ALFPm3 was successfully expressed in C. reinhardtii and secreted into the extracellular environment. Moreover, ALFPm3 extracts from the culture media of T-JaA and T-JcA showed significant inhibitory effects on the growth of V. harveyi, V. alginolyticus, V. anguillarum, and V. parahaemolyticus within 24 h. Interestingly, the inhibitory rate of c-ALFPm3 from T-JcA against four Vibrio was 2.77 to 6.23 times greater than that of a-ALFPm3 from T-JaA, indicating that the CAH1 signal peptide was more helpful in enhancing the secreted expression of the ALFPm3 peptide. Our results provided a new strategy for the secretory production of ALFPm3 with high antibacterial activity in C. reinhardtii, which could improve the application potentiality of ALFPm3 in the aquaculture industry. Full article
(This article belongs to the Special Issue Biotechnology of Algae)
Show Figures

Figure 1

16 pages, 7687 KiB  
Article
Holothurin A Inhibits RUNX1-Enhanced EMT in Metastasis Prostate Cancer via the Akt/JNK and P38 MAPK Signaling Pathway
by Sirorat Janta, Kanta Pranweerapaiboon, Pornpun Vivithanaporn, Anuchit Plubrukarn, Arthit Chairoungdua, Prachayaporn Prasertsuksri, Somjai Apisawetakan and Kulathida Chaithirayanon
Mar. Drugs 2023, 21(6), 345; https://doi.org/10.3390/md21060345 - 03 Jun 2023
Cited by 4 | Viewed by 1371
Abstract
Due to the challenge of prostate cancer (PCa) management, there has been a surge in efforts to identify more safe and effective compounds that can modulate the epithelial–mesenchymal transition (EMT) for driving metastasis. Holothurin A (HA), a triterpenoid saponin isolated from Holothuria scabra [...] Read more.
Due to the challenge of prostate cancer (PCa) management, there has been a surge in efforts to identify more safe and effective compounds that can modulate the epithelial–mesenchymal transition (EMT) for driving metastasis. Holothurin A (HA), a triterpenoid saponin isolated from Holothuria scabra, has now been characterized for its diverse biological activities. However, the mechanisms of HA in EMT-driven metastasis of human PCa cell lines has not yet been investigated. Moreover, runt-related transcription factor 1 (RUNX1) acts as an oncogene in prostate cancer, but little is known about its role in the EMT. Thus, the purpose of this study was to determine how RUNX1 influences EMT-mediated metastasis, as well as the potential effect of HA on EMT-mediated metastasis in endogenous and exogenous RUNX1 expressions of PCa cell lines. The results demonstrated that RUNX1 overexpression could promote the EMT phenotype with increased EMT markers, consequently driving metastatic migration and invasion in PC3 cell line through the activation of Akt/MAPK signaling pathways. Intriguingly, HA treatment could antagonize the EMT program in endogenous and exogenous RUNX1-expressing PCa cell lines. A decreasing metastasis of both HA-treated cell lines was evidenced through a downregulation of MMP2 and MMP9 via the Akt/P38/JNK-MAPK signaling pathway. Overall, our approach first demonstrated that RUNX1 enhanced EMT-driven prostate cancer metastasis and that HA was capable of inhibiting the EMT and metastatic processes and should probably be considered as a candidate for metastasis PCa treatment. Full article
(This article belongs to the Special Issue Bioactive Compounds from Sea Cucumbers)
Show Figures

Graphical abstract

21 pages, 1939 KiB  
Article
Pentaketides and 5-p-Hydroxyphenyl-2-pyridone Derivative from the Culture Extract of a Marine Sponge-Associated Fungus Hamigera avellanea KUFA0732
by Rotchana Klaram, Tida Dethoup, Fátima P. Machado, Luís Gales, Decha Kumla, Salar Hafez Ghoran, Emília Sousa, Sharad Mistry, Artur M. S. Silva and Anake Kijjoa
Mar. Drugs 2023, 21(6), 344; https://doi.org/10.3390/md21060344 - 02 Jun 2023
Cited by 1 | Viewed by 1408
Abstract
Five undescribed pentaketide derivatives, (R)-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1H-2-benzopyran-1-one (1), [(3S,4R)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1H-isochromen-3-yl]methyl acetate (2), (R)-5, 7-dimethoxy-3-((S)-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (4b), (S)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3H)-one ( [...] Read more.
Five undescribed pentaketide derivatives, (R)-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1H-2-benzopyran-1-one (1), [(3S,4R)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1H-isochromen-3-yl]methyl acetate (2), (R)-5, 7-dimethoxy-3-((S)-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3H)-one (4b), (S)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3H)-one (5), and a p-hydroxyphenyl-2-pyridone derivative, avellaneanone (6), were isolated together with the previously reported (R)-3-acetyl-7-hydroxy-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (3), (R)-7-hydroxy-3-((S)-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran-1(3H)-one (4a) and isosclerone (7), from the ethyl acetate extract of a culture of a marine sponge-derived fungus, Hamigera avellanea KUFA0732. The structures of the undescribed compounds were elucidated using 1D and 2D NMR, as well as high-resolution mass spectral analyses. The absolute configurations of the stereogenic carbons in 1, 4b, 5, and 6 were established by X-ray crystallographic analysis. The absolute configurations of C-3 and C-4 in 2 were determined by ROESY correlations and on the basis of their common biosynthetic origin with 1. The crude fungal extract and the isolated compounds 1, 3, 4b, 5, 6, and 7 were assayed for their growth inhibitory activity against various plant pathogenic fungi viz. Alternaria brassicicola, Bipolaris oryzae, Colletotrichum capsici, C. gloeosporiodes, Curvularia oryzae, Fusarium semitectum, Lasiodiplodia theobromae, Phytophthora palmivora, Pyricularia oryzae, Rhizoctonia oryzae and Sclerotium rolfsii. Full article
Show Figures

Graphical abstract

13 pages, 5708 KiB  
Article
Fish-Derived Protein Hydrolysates Increase Insulin Sensitivity and Alter Intestinal Microbiome in High-Fat-Induced Obese Mice
by Maria G. Daskalaki, Konstantinos Axarlis, Antiopi Tsoureki, Sofia Michailidou, Christina Efraimoglou, Ioanna Lapi, Ourania Kolliniati, Eirini Dermitzaki, Maria Venihaki, Katerina Kousoulaki, Anagnostis Argiriou and Christos Tsatsanis
Mar. Drugs 2023, 21(6), 343; https://doi.org/10.3390/md21060343 - 02 Jun 2023
Cited by 1 | Viewed by 1754
Abstract
Obesity and type 2 diabetes are characterized by low-grade systemic inflammation and glucose intolerance, which can be partially controlled with nutritional interventions. Protein-containing nutritional supplements possess health-promoting benefits. Herein, we examined the effect of dietary supplementation with protein hydrolysates derived from fish sidestreams [...] Read more.
Obesity and type 2 diabetes are characterized by low-grade systemic inflammation and glucose intolerance, which can be partially controlled with nutritional interventions. Protein-containing nutritional supplements possess health-promoting benefits. Herein, we examined the effect of dietary supplementation with protein hydrolysates derived from fish sidestreams on obesity and diabetes, utilizing a mouse model of High-Fat Diet-induced obesity and type 2 diabetes. We examined the effect of protein hydrolysates from salmon and mackerel backbone (HSB and HMB, respectively), salmon and mackerel heads (HSH and HMH, respectively), and fish collagen. The results showed that none of the dietary supplements affected weight gain, but HSH partially suppressed glucose intolerance, while HMB and HMH suppressed leptin increase in the adipose tissue. We further analyzed the gut microbiome, which contributes to the metabolic disease implicated in the development of type 2 diabetes, and found that supplementation with selected protein hydrolysates resulted in distinct changes in gut microbiome composition. The most prominent changes occurred when the diet was supplemented with fish collagen since it increased the abundance of beneficial bacteria and restricted the presence of harmful ones. Overall, the results suggest that protein hydrolysates derived from fish sidestreams can be utilized as dietary supplements with significant health benefits in the context of type 2 diabetes and diet-induced changes in the gut microbiome. Full article
Show Figures

Figure 1

25 pages, 6042 KiB  
Article
Species-Specific N-Glycomes and Methylation Patterns of Oysters Crassostrea gigas and Ostrea edulis and Their Possible Consequences for the Norovirus–HBGA Interaction
by Audrey Auger, Shin-Yi Yu, Shih-Yun Guu, Agnès Quéméner, Gabriel Euller-Nicolas, Hiromune Ando, Marion Desdouits, Françoise S. Le Guyader, Kay-Hooi Khoo, Jacques Le Pendu, Frederic Chirat and Yann Guerardel
Mar. Drugs 2023, 21(6), 342; https://doi.org/10.3390/md21060342 - 02 Jun 2023
Viewed by 1368
Abstract
Noroviruses, the major cause of acute viral gastroenteritis, are known to bind to histo-blood group antigens (HBGAs), including ABH groups and Lewis-type epitopes, which decorate the surface of erythrocytes and epithelial cells of their host tissues. The biosynthesis of these antigens is controlled [...] Read more.
Noroviruses, the major cause of acute viral gastroenteritis, are known to bind to histo-blood group antigens (HBGAs), including ABH groups and Lewis-type epitopes, which decorate the surface of erythrocytes and epithelial cells of their host tissues. The biosynthesis of these antigens is controlled by several glycosyltransferases, the distribution and expression of which varies between tissues and individuals. The use of HBGAs as ligands by viruses is not limited to humans, as many animal species, including oysters, which synthesize similar glycan epitopes that act as a gateway for viruses, become vectors for viral infection in humans. Here, we show that different oyster species synthesize a wide range of N-glycans that share histo-blood A-antigens but differ in the expression of other terminal antigens and in their modification by O-methyl groups. In particular, we show that the N-glycans isolated from Crassostrea gigas and Ostrea edulis exhibit exquisite methylation patterns in their terminal N-acetylgalactosamine and fucose residues in terms of position and number, adding another layer of complexity to the post-translational glycosylation modifications of glycoproteins. Furthermore, modeling of the interactions between norovirus capsid proteins and carbohydrate ligands strongly suggests that methylation has the potential to fine-tune the recognition events of oysters by virus particles. Full article
(This article belongs to the Special Issue Marine Glycomics 2nd Edition)
Show Figures

Figure 1

13 pages, 2392 KiB  
Article
Production of Ethyl-agarobioside, a Novel Skin Moisturizer, by Mimicking the Alcoholysis from the Japanese Sake-Brewing Process
by Sun-Hee Lee, Eun Ju Yun, Na Ree Han, Inho Jung, Jeffrey G. Pelton, Jae-Eun Lee, Nam Joo Kang, Yong-Su Jin and Kyoung Heon Kim
Mar. Drugs 2023, 21(6), 341; https://doi.org/10.3390/md21060341 - 01 Jun 2023
Cited by 1 | Viewed by 1301
Abstract
Agarobiose (AB; d-galactose-β-1,4-AHG), produced by one-step acid hydrolysis of agarose of red seaweed, is considered a promising cosmetic ingredient due to its skin-moisturizing activity. In this study, the use of AB as a cosmetic ingredient was found to be hampered due to [...] Read more.
Agarobiose (AB; d-galactose-β-1,4-AHG), produced by one-step acid hydrolysis of agarose of red seaweed, is considered a promising cosmetic ingredient due to its skin-moisturizing activity. In this study, the use of AB as a cosmetic ingredient was found to be hampered due to its instability at high temperature and alkaline pH. Therefore, to increase the chemical stability of AB, we devised a novel process to synthesize ethyl-agarobioside (ethyl-AB) from the acid-catalyzed alcoholysis of agarose. This process mimics the generation of ethyl α-glucoside and glyceryl α-glucoside by alcoholysis in the presence of ethanol and glycerol during the traditional Japanese sake-brewing process. Ethyl-AB also showed in vitro skin-moisturizing activity similar to that of AB, but showed higher thermal and pH stability than AB. This is the first report of ethyl-AB, a novel compound produced from red seaweed, as a functional cosmetic ingredient with high chemical stability. Full article
Show Figures

Graphical abstract

45 pages, 859 KiB  
Review
Microalgae, Seaweeds and Aquatic Bacteria, Archaea, and Yeasts: Sources of Carotenoids with Potential Antioxidant and Anti-Inflammatory Health-Promoting Actions in the Sustainability Era
by Paula Mapelli-Brahm, Patricia Gómez-Villegas, Mariana Lourdes Gonda, Antonio León-Vaz, Rosa León, Jennifer Mildenberger, Céline Rebours, Verónica Saravia, Silvana Vero, Eugenia Vila and Antonio J. Meléndez-Martínez
Mar. Drugs 2023, 21(6), 340; https://doi.org/10.3390/md21060340 - 01 Jun 2023
Cited by 10 | Viewed by 5497
Abstract
Carotenoids are a large group of health-promoting compounds used in many industrial sectors, such as foods, feeds, pharmaceuticals, cosmetics, nutraceuticals, and colorants. Considering the global population growth and environmental challenges, it is essential to find new sustainable sources of carotenoids beyond those obtained [...] Read more.
Carotenoids are a large group of health-promoting compounds used in many industrial sectors, such as foods, feeds, pharmaceuticals, cosmetics, nutraceuticals, and colorants. Considering the global population growth and environmental challenges, it is essential to find new sustainable sources of carotenoids beyond those obtained from agriculture. This review focuses on the potential use of marine archaea, bacteria, algae, and yeast as biological factories of carotenoids. A wide variety of carotenoids, including novel ones, were identified in these organisms. The role of carotenoids in marine organisms and their potential health-promoting actions have also been discussed. Marine organisms have a great capacity to synthesize a wide variety of carotenoids, which can be obtained in a renewable manner without depleting natural resources. Thus, it is concluded that they represent a key sustainable source of carotenoids that could help Europe achieve its Green Deal and Recovery Plan. Additionally, the lack of standards, clinical studies, and toxicity analysis reduces the use of marine organisms as sources of traditional and novel carotenoids. Therefore, further research on the processing of marine organisms, the biosynthetic pathways, extraction procedures, and examination of their content is needed to increase carotenoid productivity, document their safety, and decrease costs for their industrial implementation. Full article
(This article belongs to the Special Issue Marine Bioactive Compounds against Oxidative Stress and Inflammation)
Show Figures

Graphical abstract

16 pages, 2717 KiB  
Article
Impact of Enzymatically Extracted High Molecular Weight Fucoidan on Lipopolysaccharide-Induced Endothelial Activation and Leukocyte Adhesion
by Nora Kirsten, Julia Ohmes, Maria Dalgaard Mikkelsen, Thuan Thi Nguyen, Martina Blümel, Fanlu Wang, Deniz Tasdemir, Andreas Seekamp, Anne S. Meyer and Sabine Fuchs
Mar. Drugs 2023, 21(6), 339; https://doi.org/10.3390/md21060339 - 31 May 2023
Cited by 1 | Viewed by 1329
Abstract
The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, [...] Read more.
The endothelial cell lining creates an interface between circulating blood and adjoining tissue and forms one of the most critical barriers and targets for therapeutical intervention. Recent studies suggest that fucoidans, sulfated and fucose-rich polysaccharides from brown seaweed, show multiple promising biological effects, including anti-inflammatory properties. However, their biological activity is determined by chemical characteristics such as molecular weight, sulfation degree, and molecular structure, which vary depending on the source, species, and harvesting and isolation method. In this study, we investigated the impact of high molecular weight (HMW) fucoidan extract on endothelial cell activation and interaction with primary monocytes (MNCs) in lipopolysaccharide (LPS)-induced inflammation. Gentle enzyme-assisted extraction combined with fractionation by ion exchange chromatography resulted in well-defined and pure fucoidan fractions. FE_F3, with a molecular weight ranging from 110 to 800 kDa and a sulfate content of 39%, was chosen for further investigation of its anti-inflammatory potential. We observed that along with higher purity of fucoidan fractions, the inflammatory response in endothelial mono- and co-cultures with MNCs was reduced in a dose-dependent manner when testing two different concentrations. This was demonstrated by a decrease in IL-6 and ICAM-1 on gene and protein levels and a reduced gene expression of TLR-4, GSK3β and NF-kB. Expression of selectins and, consequently, the adhesion of monocytes to the endothelial monolayer was reduced after fucoidan treatment. These data indicate that the anti-inflammatory effect of fucoidans increases with their purity and suggest that fucoidans might be useful in limiting the inflammatory response of endothelial cells in cases of LPS-induced bacterial infection. Full article
(This article belongs to the Special Issue Bioactive Polysaccharides from Seaweeds)
Show Figures

Graphical abstract

Previous Issue
Next Issue
Back to TopTop