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Mar. Drugs, Volume 22, Issue 3 (March 2024) – 43 articles

Cover Story (view full-size image): Indole is a privileged scaffold in various molecules isolated from marine organisms such as fungi, algae, corals, and sponges. Among these, indole alkaloids have shown a wide range of pharmacological properties, including anti-inflammatory, antiviral, and anticancer properties. In this sense, they can be used to produce potential drugs for human diseases. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering the most common chemical structures, their promising therapeutic applications, and the general synthetic routes developed during the last few years. View this paper
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19 pages, 6974 KiB  
Article
Purification of an Acidic Polysaccharide with Anticoagulant Activity from the Marine Sponge Sarcotragus spinosulus
by Gabriele Nieddu, Gabriele Obino, Cristina Ciampelli, Antonio Brunetti, Tiziana Cubeddu, Renata Manconi, Giacinta Angela Stocchino, Giovanni Andrea Deiana, Marilena Formato and Antonio Junior Lepedda
Mar. Drugs 2024, 22(3), 139; https://doi.org/10.3390/md22030139 - 21 Mar 2024
Viewed by 738
Abstract
Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus [...] Read more.
Thromboembolic conditions are the most common cause of death in developed countries. Anticoagulant therapy is the treatment of choice, and heparinoids and warfarin are the most adopted drugs. Sulphated polysaccharides extracted from marine organisms have been demonstrated to be effective alternatives, blocking thrombus formation by inhibiting some factors involved in the coagulation cascade. In this study, four acidic glycan fractions from the marine sponge Sarcotragus spinosulus were purified by anion-exchange chromatography, and their anticoagulant properties were investigated through APTT and PT assays and compared with both standard glycosaminoglycans and holothurian sulphated polysaccharides. Moreover, their topographic localization was assessed through histological analysis, and their cytocompatibility was tested on a human fibroblast cell line. A positive correlation between the amount of acid glycans and the inhibitory effect towards both the intrinsic and extrinsic coagulation pathways was observed. The most effective anticoagulant activity was shown by a highly charged fraction, which accounted for almost half (about 40%) of the total hexuronate-containing polysaccharides. Its preliminary structural characterization, performed through infrared spectroscopy and nuclear magnetic resonance, suggested that it may consist of a fucosylated chondroitin sulphate, whose unique structure may be responsible for the anticoagulant activity reported herein for the first time. Full article
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18 pages, 4695 KiB  
Article
Maximizing Polysaccharides and Phycoerythrin in Porphyridium purpureum via the Addition of Exogenous Compounds: A Response-Surface-Methodology Approach
by Sanjiong Yi, Ai-Hua Zhang, Jianke Huang, Ting Yao, Bo Feng, Xinghu Zhou, Yadong Hu and Mingxuan Pan
Mar. Drugs 2024, 22(3), 138; https://doi.org/10.3390/md22030138 - 21 Mar 2024
Viewed by 632
Abstract
Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) [...] Read more.
Phycoerythrin and polysaccharides have significant commercial value in medicine, cosmetics, and food industries due to their excellent bioactive functions. To maximize the production of biomass, phycoerythrin, and polysaccharides in Porphyridium purpureum, culture media were supplemented with calcium gluconate (CG), magnesium gluconate (MG) and polypeptides (BT), and their optimal amounts were determined using the response surface methodology (RSM) based on three single-factor experiments. The optimal concentrations of CG, MG, and BT were determined to be 4, 12, and 2 g L−1, respectively. The RSM-based models indicated that biomass and phycoerythrin production were significantly affected only by MG and BT, respectively. However, polysaccharide production was significantly affected by the interactions between CG and BT and those between MG and BT, with no significant effect from BT alone. Using the optimized culture conditions, the maximum biomass (5.97 g L−1), phycoerythrin (102.95 mg L−1), and polysaccharide (1.42 g L−1) concentrations met and even surpassed the model-predicted maximums. After optimization, biomass, phycoerythrin, and polysaccharides concentrations increased by 132.3%, 27.97%, and 136.67%, respectively, compared to the control. Overall, this study establishes a strong foundation for the highly efficient production of phycoerythrin and polysaccharides using P. purpureum. Full article
(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products)
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14 pages, 4776 KiB  
Article
Effect of Ishige okamurae Extract on Osteoclastogenesis In Vitro and In Vivo
by Su-Hyeon Cho, Hyun-Soo Kim, Juhee Ahn, Bomi Ryu, Jun-Geon Jea, Kyubin Lee, Kyunghwan Kim, Ginnae Ahn, WonWoo Lee, Kyung-Min Choi and Kil-Nam Kim
Mar. Drugs 2024, 22(3), 137; https://doi.org/10.3390/md22030137 - 20 Mar 2024
Viewed by 721
Abstract
We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, [...] Read more.
We demonstrated the effect of Ishige okamurae extract (IOE) on the receptor activator of nuclear factor-κB ligand (RANKL)-promoted osteoclastogenesis in RAW 264.7 cells and confirmed that IOE inhibited RANKL-induced tartrate-resistant acid phosphatase (TRAP) activity and osteoclast differentiation. IOE inhibited protein expression of TRAP, metallopeptidase-9 (MMP-9), the calcitonin receptor (CTR), and cathepsin K (CTK). IOE treatment suppressed the expression of activated T cell cytoplasmic 1 and activator protein-1, thus controlling the expression of osteoclast-related factors. Moreover, IOE significantly reduced RANKL-phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). It also reduced the RANKL-induced phosphorylation of NF-κB and nuclear translocation of p65. IOE inhibited Dex-induced bone loss and osteoclast-related gene expression in zebrafish larvae. HPLC analysis shows that IOE consists of 3.13% and 3.42% DPHC and IPA, respectively. Our results show that IOE has inhibitory effects on osteoclastogenesis in vitro and in vivo and is a potential therapeutic for osteoporosis. Full article
(This article belongs to the Section Marine Pharmacology)
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21 pages, 8244 KiB  
Review
Towards the Exploration and Evolution of Insulin-like Venoms in Actiniaria (Sea anemones)
by Alonso Delgado, Kyle S. Sozanski and Marymegan Daly
Mar. Drugs 2024, 22(3), 136; https://doi.org/10.3390/md22030136 - 20 Mar 2024
Viewed by 802
Abstract
Recent studies have elucidated the diversity of genes encoding venom in Sea anemones. However, most of those genes are yet to be explored in an evolutionary context. Insulin is a common peptide across metazoans and has been coopted into a predatory venom [...] Read more.
Recent studies have elucidated the diversity of genes encoding venom in Sea anemones. However, most of those genes are yet to be explored in an evolutionary context. Insulin is a common peptide across metazoans and has been coopted into a predatory venom in many venomous lineages. In this study, we focus on the diversity of insulin-derived venoms in Sea anemones and on elucidating their evolutionary history. We sourced data for 34 species of Sea anemones and found sequences belonging to two venom families which have Insulin PFAM annotations. Our findings show that both families have undergone duplication events. Members of each of the independently evolving clades have consistent predicted protein structures and distinct dN/dS values. Our work also shows that sequences allied with VP302 are part of a multidomain venom contig and have experienced a secondary gain into the venom system of cuticulate Sea anemones. Full article
(This article belongs to the Section Marine Toxins)
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15 pages, 11095 KiB  
Article
Study on the Anti-Mycobacterium marinum Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives
by Qian-Qian Jing, Jun-Na Yin, Ya-Jie Cheng, Qun Zhang, Xi-Zhen Cao, Wei-Feng Xu, Chang-Lun Shao and Mei-Yan Wei
Mar. Drugs 2024, 22(3), 135; https://doi.org/10.3390/md22030135 - 16 Mar 2024
Viewed by 912
Abstract
With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid [...] Read more.
With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. Mycobacterium marinum, as a model organism of Mycobacterium tuberculosis, can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti-M. marinum activity was evaluated in vitro. Derivatives 12, 19, 20 and 22 exhibited promising activity with MIC90 values of 80, 90, 80 and 80 μM, respectively. The preliminary structure–activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that 12 markedly inhibited the survival of M. marinum and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that 12 is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance. Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products)
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23 pages, 3019 KiB  
Review
Recent Developments in Bio-Ink Formulations Using Marine-Derived Biomaterials for Three-Dimensional (3D) Bioprinting
by Zied Khiari
Mar. Drugs 2024, 22(3), 134; https://doi.org/10.3390/md22030134 - 16 Mar 2024
Viewed by 872
Abstract
3D bioprinting is a disruptive, computer-aided, and additive manufacturing technology that allows the obtention, layer-by-layer, of 3D complex structures. This technology is believed to offer tremendous opportunities in several fields including biomedical, pharmaceutical, and food industries. Several bioprinting processes and bio-ink materials have [...] Read more.
3D bioprinting is a disruptive, computer-aided, and additive manufacturing technology that allows the obtention, layer-by-layer, of 3D complex structures. This technology is believed to offer tremendous opportunities in several fields including biomedical, pharmaceutical, and food industries. Several bioprinting processes and bio-ink materials have emerged recently. However, there is still a pressing need to develop low-cost sustainable bio-ink materials with superior qualities (excellent mechanical, viscoelastic and thermal properties, biocompatibility, and biodegradability). Marine-derived biomaterials, including polysaccharides and proteins, represent a viable and renewable source for bio-ink formulations. Therefore, the focus of this review centers around the use of marine-derived biomaterials in the formulations of bio-ink. It starts with a general overview of 3D bioprinting processes followed by a description of the most commonly used marine-derived biomaterials for 3D bioprinting, with a special attention paid to chitosan, glycosaminoglycans, alginate, carrageenan, collagen, and gelatin. The challenges facing the application of marine-derived biomaterials in 3D bioprinting within the biomedical and pharmaceutical fields along with future directions are also discussed. Full article
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16 pages, 1491 KiB  
Article
Novel [1,3,4]Thiadiazole[3,2-a]pyrimidin-5-ones as Promising Biofilm Dispersal Agents against Relevant Gram-Positive and Gram-Negative Pathogens
by Daniela Carbone, Camilla Pecoraro, Fabio Scianò, Valentina Catania, Domenico Schillaci, Barbara Manachini, Stella Cascioferro, Patrizia Diana and Barbara Parrino
Mar. Drugs 2024, 22(3), 133; https://doi.org/10.3390/md22030133 - 15 Mar 2024
Viewed by 765
Abstract
Biofilm-associated infections pose significant challenges in healthcare settings due to their resistance to conventional antimicrobial therapies. In the last decade, the marine environment has been a precious source of bioactive molecules, including numerous derivatives with antibiofilm activity. In this study, we reported the [...] Read more.
Biofilm-associated infections pose significant challenges in healthcare settings due to their resistance to conventional antimicrobial therapies. In the last decade, the marine environment has been a precious source of bioactive molecules, including numerous derivatives with antibiofilm activity. In this study, we reported the synthesis and the biological evaluation of a new series of twenty-two thiadiazopyrimidinone derivatives obtained by using a hybridization approach combining relevant chemical features of two important classes of marine compounds: nortopsentin analogues and Essramycin derivatives. The synthesized compounds were in vitro tested for their ability to inhibit biofilm formation and to disrupt mature biofilm in various bacterial strains. Among the tested compounds, derivative 8j exhibited remarkable dispersal activity against preformed biofilms of relevant Gram-positive and Gram-negative pathogens, as well as towards the fungus Candida albicans, showing BIC50 values ranging from 17 to 40 µg/mL. Furthermore, compound 8j was in vivo assayed for its toxicity and the anti-infective effect in a Galleria mellonella model. The results revealed a promising combination of anti-infective properties and a favorable toxicity profile for the treatment of severe chronic biofilm-mediated infections. Full article
(This article belongs to the Special Issue Marine Drug Research in Italy)
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36 pages, 11980 KiB  
Review
Marine Bromotyrosine Derivatives in Spotlight: Bringing Discoveries and Biological Significance
by Paula Ferreira Montenegro, Giang Nam Pham, Fatouma Mohamed Abdoul-Latif, Elisabeth Taffin-de-Givenchy and Mohamed Mehiri
Mar. Drugs 2024, 22(3), 132; https://doi.org/10.3390/md22030132 - 14 Mar 2024
Viewed by 825
Abstract
The Verongida order comprises several sponge families, such as Aplysinellidae, Aplysinidae, Ianthellidae, and Pseudoceratinidae, reported for producing bromotyrosine-derived compounds. First identified in 1913, bromotyrosine derivatives have since captivated interest notably for their antitumor and antimicrobial properties. To date, over 360 bromotyrosine derivatives have [...] Read more.
The Verongida order comprises several sponge families, such as Aplysinellidae, Aplysinidae, Ianthellidae, and Pseudoceratinidae, reported for producing bromotyrosine-derived compounds. First identified in 1913, bromotyrosine derivatives have since captivated interest notably for their antitumor and antimicrobial properties. To date, over 360 bromotyrosine derivatives have been reported. Our review focuses specifically on bromotyrosine derivatives newly reported from 2004 to 2023, by summarizing current knowledge about their chemical diversity and their biological activities. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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21 pages, 2683 KiB  
Article
Anti-Inflammatory Activity of Cyanobacteria Pigment Extracts: Physiological Free Radical Scavenging and Modulation of iNOS and LOX Activity
by Lécia Rodrigues, Janaína Morone, Guilherme Scotta Hentschke, Vitor Vasconcelos and Graciliana Lopes
Mar. Drugs 2024, 22(3), 131; https://doi.org/10.3390/md22030131 - 12 Mar 2024
Viewed by 1717
Abstract
Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE [...] Read more.
Cyanobacteria are among the oldest organisms colonizing Earth. Their great biodiversity and ability to biosynthesize secondary metabolites through a variety of routes makes them attractive resources for biotechnological applications and drug discovery. In this pioneer study, four filamentous cyanobacteria (Cephalothrix lacustris LEGE 15493, Leptolyngbya boryana LEGE 15486, Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479) were explored for their anti-inflammatory potential in cell and cell-free in vitro bioassays, involving different inflammatory mediators and enzymes. Extracts of different polarities were sequentially prepared and chemically characterized for their content of phycobiliproteins (PBPs) and carotenoids. HPLC-PDA analysis of the acetone extracts revealed β-carotene to be the dominant carotenoid (18.4–44.3 mg/g) and zeaxanthin as the dominant xanthophyll (52.7–192.9 mg/g), with Leptothoe sp. LEGE 11479 and Nodosilinea nodulosa LEGE 06104, respectively, being the richest strains. The PBP profile was in accordance with the color presented by the aqueous extracts, with Leptolyngbya boryana LEGE 15486 being the richest in phycocyanin (204.5 μg/mg) and Leptothoe sp. LEGE 11479 the richest in phycoerythrin (78.5 μg/mg). Aqueous extracts were more effective in superoxide anion radical scavenging, while acetone ones were more effective in scavenging nitric oxide radical (NO) and in inhibiting lipoxygenase. Acetone extracts also reduced NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with the mechanistic study suggesting a downregulation of the inducible nitric oxide synthase expression. Nodosilinea nodulosa LEGE 06104 and Leptothoe sp. LEGE 11479 acetone extracts presented the lowest IC50 values for the mentioned assays, pointing them out as promising resources for the development of new multi-target anti-inflammatory therapies. Full article
(This article belongs to the Special Issue Antiphotoaging and Photoprotective Compounds from Marine Environments)
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27 pages, 3477 KiB  
Article
Antioxidant Activity, Inhibition of Intestinal Cancer Cell Growth and Polyphenolic Compounds of the Seagrass Posidonia oceanica’s Extracts from Living Plants and Beach Casts
by Alkistis Kevrekidou, Andreana N. Assimopoulou, Varvara Trachana, Dimitrios Stagos and Paraskevi Malea
Mar. Drugs 2024, 22(3), 130; https://doi.org/10.3390/md22030130 - 11 Mar 2024
Viewed by 880
Abstract
The aim of the present study was to investigate the use of Posidonia oceanica for making products beneficial for human health. Firstly, we demonstrated that the antioxidant defense (i.e., SOD and APX activity) of P. oceanica’s living leaves (LP) has low efficacy, [...] Read more.
The aim of the present study was to investigate the use of Posidonia oceanica for making products beneficial for human health. Firstly, we demonstrated that the antioxidant defense (i.e., SOD and APX activity) of P. oceanica’s living leaves (LP) has low efficacy, as they partly neutralize the produced H2O2. However, high H2O2 levels led LP to produce, as a response to oxidative stress, high phenolic content, including chicoric acid, p-coumaric acid, caftaric acid, trans-cinnamic and rutin hydrate, as shown by UHPLC-DAD analysis. In addition, LP extracts inhibited intestinal cancer cell proliferation. Moreover, P. oceanica’s beach casts consisting of either Wet ‘Necromass’ (WNP) or Dry ‘Necromass’ (DNP) were used for preparing extracts. Both DNP and WNP exhibited antioxidant and antiproliferative activities, although lower as compared to those of LP extracts. Although both P. oceanica’s meadows and beach casts are considered priority habitats in the Mediterranean Sea due to their high ecological value, legislation framework for beach casts forbidding their removal is still missing. Our results suggested that both LP and DNP could be utilized for the production of high-added value products promoting human health, provided that a sustainability management strategy would be applied for P. oceanica’s meadows and beach casts. Full article
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18 pages, 535 KiB  
Review
A Review of Cyclic Imines in Shellfish: Worldwide Occurrence, Toxicity and Assessment of the Risk to Consumers
by Sarah C. Finch, D. Tim Harwood, Michael J. Boundy and Andrew I. Selwood
Mar. Drugs 2024, 22(3), 129; https://doi.org/10.3390/md22030129 - 11 Mar 2024
Cited by 1 | Viewed by 968
Abstract
Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine [...] Read more.
Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine microalgal species and are characterized by the rapid death that they induce when injected into mice. Cyclic imines have been detected in a range of shellfish species collected from all over the world, which raises the question as to whether they present a food safety risk. The European Food Safety Authority (EFSA) considers them to be an emerging food safety issue, and in this review, the risk posed by these toxins to shellfish consumers is assessed by collating all available occurrence and toxicity data. Except for pinnatoxins, the risk posed to human health by the cyclic imines appears low, although this is based on only a limited dataset. For pinnatoxins, two different health-based guidance values have been proposed at which the concentration should not be exceeded in shellfish (268 and 23 µg PnTX/kg shellfish flesh), with the discrepancy caused by the application of different uncertainty factors. Pinnatoxins have been recorded globally in multiple shellfish species at concentrations of up to 54 times higher than the lower guidance figure. Despite this observation, pinnatoxins have not been associated with recorded human illness, so it appears that the lower guidance value may be conservative. However, there is insufficient data to generate a more robust guidance value, so additional occurrence data and toxicity information are needed. Full article
(This article belongs to the Special Issue Emerging Toxins Accumulation in Shellfish)
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19 pages, 3674 KiB  
Article
Isolation and Purification of Chitosan Oligosaccharides (Mw ≤ 1000) and Their Protective Effect on Acute Liver Injury Caused by CCl4
by Kai Wang, Dawei Yu, Yan Bai, Hua Cao, Jiao Guo and Zhengquan Su
Mar. Drugs 2024, 22(3), 128; https://doi.org/10.3390/md22030128 - 08 Mar 2024
Viewed by 885
Abstract
Chitosan oligosaccharides are the degradation products of chitin obtained from the shell extracts of shrimps and crabs. Compared with chitosan, chitosan oligosaccharides have better solubility and a wider application range. In this study, high-molecular-weight chitosan oligosaccharides (COST, chitosan oligosaccharides, MW ≤ 1000) were [...] Read more.
Chitosan oligosaccharides are the degradation products of chitin obtained from the shell extracts of shrimps and crabs. Compared with chitosan, chitosan oligosaccharides have better solubility and a wider application range. In this study, high-molecular-weight chitosan oligosaccharides (COST, chitosan oligosaccharides, MW ≤ 1000) were isolated and purified by a GPC gel column, and the molecular weight range was further reduced to obtain high-purity and low-molecular-weight chitosan (COS46). Compared with COST, COS46 is better at inhibiting CCl4-induced cell death, improving cell morphology, reducing ALT content, and improving cell antioxidant capacity. The effects of COST and COS46 on CCl4-induced acute liver injury were further verified in mice. Both COS46 and COST improved the appearance of the liver induced by CCl4, decreased the levels of ALT and AST in serum, and decreased the oxidation/antioxidant index in the liver. From the liver pathological section, the effect of COS46 was better. In addition, some indicators of COS46 showed a dose-dependent effect. In conclusion, compared with COST, low-molecular-weight COS46 has better antioxidant capacity and a better therapeutic effect on CCl4-induced acute liver injury. Full article
(This article belongs to the Special Issue Application of Marine Chitin and Chitosan 3rd Edition)
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15 pages, 4453 KiB  
Article
Induction of Autophagy by Extract from Corydalis heterocarpa for Skin Anti-Aging
by Kyeong Eun Yang, Soo-Bin Nam, Ga-Eun Lee, Gabsik Yang, Mee-Hyun Lee, Geul Bang, Jung Hoon Choi, Yong-Yeon Cho and Cheol-Jung Lee
Mar. Drugs 2024, 22(3), 127; https://doi.org/10.3390/md22030127 - 08 Mar 2024
Viewed by 934
Abstract
The extracts of Corydalis heterocarpa, a salt-tolerant plant, exhibit diverse physiological properties, including anti-inflammatory, anticancer, and antiadipogenic effects. However, the anti-aging effects of C. heterocarpa extract (CHE) on human skin cells have not yet been investigated. In the present study, we determined [...] Read more.
The extracts of Corydalis heterocarpa, a salt-tolerant plant, exhibit diverse physiological properties, including anti-inflammatory, anticancer, and antiadipogenic effects. However, the anti-aging effects of C. heterocarpa extract (CHE) on human skin cells have not yet been investigated. In the present study, we determined that CHE inhibited senescence-associated β-galactosidase (SA-β-gal)-stained senescent human dermal fibroblasts (HDFs). Furthermore, CHE markedly suppressed the expression of major regulatory proteins involved in senescence, including p53, p21, and caveolin-1. Interestingly, CHE promoted autophagic flux, as confirmed by the formation of microtubule-associated protein 1 light chain 3B (LC3B) puncta and lysosomal activity. Notably, using RNA sequencing (RNA-seq), we showed that CHE selectively regulated the gene expression of leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1), an important regulator of autophagy. The adenosine-monophosphate activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway, which is essential for autophagy regulation, was also modulated by CHE. LRSAM1 depletion not only inhibited LC3B expression but also decreased the autophagy flux induced by CHE. Moreover, the knockdown of LRSAM1 suppressed the reversal of CHE-induced senescence in old HDFs. Collectively, our study has revealed the rejuvenating effects and molecular mechanisms of CHE, suggesting that CHE may be a promising anti-aging agent. Full article
(This article belongs to the Special Issue Marine Drug Research in Korea II)
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58 pages, 13683 KiB  
Review
Current Status of Indole-Derived Marine Natural Products: Synthetic Approaches and Therapeutic Applications
by Sergio Fernández, Virginia Arnáiz, Daniel Rufo and Yolanda Arroyo
Mar. Drugs 2024, 22(3), 126; https://doi.org/10.3390/md22030126 - 06 Mar 2024
Viewed by 1240
Abstract
Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family [...] Read more.
Indole is a versatile pharmacophore widely distributed in bioactive natural products. This privileged scaffold has been found in a variety of molecules isolated from marine organisms such as algae and sponges. Among these, indole alkaloids represent one of the biggest, most promising family of compounds, having shown a wide range of pharmacological properties including anti-inflammatory, antiviral, and anticancer activities. The aim of this review is to show the current scenario of marine indole alkaloid derivatives, covering not only the most common chemical structures but also their promising therapeutic applications as well as the new general synthetic routes developed during the last years. Full article
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24 pages, 7591 KiB  
Article
Effects of Polymannuronic Acid on the Intestinal Microbiota in Mice after Long-Term Intragastric Administration
by E Zhang, Qiang Wei, Xia Li and Shuliang Song
Mar. Drugs 2024, 22(3), 125; https://doi.org/10.3390/md22030125 - 06 Mar 2024
Viewed by 800
Abstract
Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by [...] Read more.
Polymannuronic acid (PM) is an alginate oligosaccharide derived from brown algae with a characterized structure and excellent biological activities. Herein, mice were given different doses of PM through 30-day-long-term intragastric administration, and the contents of the jejunum, ileum, and colon were analyzed by 16S rRNA gene sequencing technology for microbial diversity, and relevant experiments were verified according to the analysis results so as to comprehensively evaluate the effects of PM on the intestinal flora. The PM (400 mg/kg and 100 mg/kg) could regulate the microflora balance at the phylum level and increase the microflora richness in the jejunum, ileum, and colon of the mice. The PM could induce more strains that are negatively correlated with Escherichia, thereby reducing the relative abundance of Escherichia. Analysis of bacterial function showed that high and low doses of PM could promote lipid metabolism in the bacterial communities. Moreover, the PM could reduce serum total cholesterol and cholesterol ester levels in a concentration-dependent manner. High-dose PM could lead to colonic intestinal inflammation by increasing the relative abundance of multiple bacterial groups in the jejunum, ileum, and colon. Moreover, high-dose PM could increase lipopolysaccharide-binding protein and interleukin-1β levels. Therefore, the dose of PM plays an important role in its efficacy, and its biological activity is dosedifferent. Full article
(This article belongs to the Special Issue Polysaccharides from Marine Environment)
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18 pages, 2620 KiB  
Article
Microencapsulation of Lactobacillus plantarum with Improved Survivability Using Pufferfish Skin Gelatin-Based Wall Materials
by Honghui Guo, Yelin Zhou, Quanling Xie, Hui Chen, Yiping Zhang, Zhuan Hong, Sijin Chen and Ming’en Zhang
Mar. Drugs 2024, 22(3), 124; https://doi.org/10.3390/md22030124 - 05 Mar 2024
Viewed by 896
Abstract
To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined [...] Read more.
To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined with PSG on L. plantarum. The experimental results of spray-drying with an inlet temperature of 120 °C and an outlet temperature of 80 °C, storage at 4 °C for 6 months, simulated digestion, and turbidity indicated that PSG/SC had better stability and encapsulation effects and was more suitable to encapsulate L. plantarum than PSG/SPI and PSG/WPI. The optimum preparation conditions for L. plantarum microcapsules were a PSG/SC mass ratio of 2:1, an SC concentration of 20 g/L, and a cell concentration of 10 g/L. The encapsulation efficiency of the obtained microcapsules was 95.0%, and the survival rate was 94.2% in simulated gastric fluid for 2 h and 98.0% in simulated intestinal fluid for 2 h. Amino acid composition analysis exhibited that the imino acid and aspartic acid contents of PSG were 27.98 and 26.16 g/100 g protein, respectively, which was much higher than commercial bovine gelatin. This characteristic was favorable to the high encapsulation efficiency and stability of microcapsules. In vitro release experiments showed that the PSG/SC microcapsules did not disintegrate in simulated gastric fluid for 2 h but could completely release in simulated intestinal fluid for 2 h, which can maintain the high survivability of L. plantarum in simulated digestion. In general, this study demonstrated that microcapsules using PSG/SC as wall materials can effectively improve the survivability of probiotics and have great potential for application in probiotic products. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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17 pages, 1637 KiB  
Article
Algae-Based Supplements Claiming Weight Loss Properties: Authenticity Control and Scientific-Based Evidence on Their Effectiveness
by Fátima Fernandes, Raquel Martins, Mariana Barbosa and Patrícia Valentão
Mar. Drugs 2024, 22(3), 123; https://doi.org/10.3390/md22030123 - 05 Mar 2024
Viewed by 1074
Abstract
The worldwide prevalence of obesity impacts more than 600 million adults. Successfully managing weight is effective in reducing the risk of chronic diseases, but sustaining long-term weight loss remains a challenge. Although there are supplements based on algae that claim to aid in [...] Read more.
The worldwide prevalence of obesity impacts more than 600 million adults. Successfully managing weight is effective in reducing the risk of chronic diseases, but sustaining long-term weight loss remains a challenge. Although there are supplements based on algae that claim to aid in weight loss, there is a notable scarcity of scientific evidence supporting their effectiveness, and their regular consumption safety remains inadequately addressed. In this work, commercially available Arthrospira (Spirulina) platensis Gomont and/or Fucus vesiculosus L. supplements showed moderate capacity to inhibit the activity of carbohydrate-metabolizing enzymes, and to scavenge biologically relevant reactive species. IC25 values varying between 4.54 ± 0.81 and 66.73 ± 5.91 µg of dry extract/mL and between 53.74 ± 8.42 and 1737.96 ± 98.26 µg of dry extract/mL were obtained for α-glucosidase and aldose reductase, respectively. A weaker effect towards α-amylase activity was observed, with a maximum activity of the extracts not going beyond 33%, at the highest concentrations tested. Spirulina extracts showed generally better effects than those from F. vesiculosus. Similar results were observed concerning the antiradical capacity. In a general way, the extracts were able to intercept the in vitro-generated reactive species nitric oxide (NO) and superoxide anion (O2•−) radicals, with better results for O2•−scavenging with the spirulina samples (IC25 values of 67.16 and 122.84 µg of dry extract/mL). Chemically, similar pigment profiles were observed between spirulina supplements and the authenticated counterpart. However, fucoxanthin, the chemotaxonomic marker of brown seaweeds, was not found in F. vesiculosus samples, pointing to the occurrence of a degradation phenomenon before, during, or after raw material processing. Our findings can contribute to providing data to allow regulatory entities (e.g., EFSA and FDA) to better rule these products in a way that can benefit society. Full article
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11 pages, 5294 KiB  
Communication
First Report of Pinnatoxin-G (PnTX-G) in a Marine–Coastal Area of the Adriatic Sea Associated with the Presence of the Dinoflagellate Vulcanodinium rugosum
by Monica Cangini, Sonia Dall’Ara, Silva Rubini, Barbara Bertasi, Paolo Rizzi, Giovanni Dell’Orfano, Stefania Milandri, Stefano Manfredini, Erika Baldini and Silvia Vertuani
Mar. Drugs 2024, 22(3), 122; https://doi.org/10.3390/md22030122 - 05 Mar 2024
Viewed by 901
Abstract
This study reports the first detection of the marine neurotoxin pinnatoxin-G (PnTX-G) in clams collected in the northwestern Adriatic Sea (Italy). It also represents the first report of the potential toxin-producing dinoflagellate, Vulcanodinium rugosum, in Italian seas. This result, from the coasts [...] Read more.
This study reports the first detection of the marine neurotoxin pinnatoxin-G (PnTX-G) in clams collected in the northwestern Adriatic Sea (Italy). It also represents the first report of the potential toxin-producing dinoflagellate, Vulcanodinium rugosum, in Italian seas. This result, from the coasts of the Emilia-Romagna Region, indicates a successful colonization process, reflecting conditions in France where V. rugosum was initially documented. In this case, the concentration of PnTXs was very low, making further sampling necessary to fully understand the extent of the phenomenon. Discussions on the need to obtain more data to support a proper risk assessment and the need to implement a monitoring program that includes emerging marine biotoxins are also included. Full article
(This article belongs to the Special Issue Emerging Toxins Accumulation in Shellfish)
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14 pages, 1716 KiB  
Article
Mycosporine-like Amino Acids in Palmaria palmata (Rhodophyta): Specific Implication of Usujirene in Photoprotection
by Fanny Lalegerie, Valérie Stiger-Pouvreau and Solène Connan
Mar. Drugs 2024, 22(3), 121; https://doi.org/10.3390/md22030121 - 05 Mar 2024
Viewed by 919
Abstract
The effect of UV radiation on the accumulation of mycosporine-like amino acids (MAAs) and pigments was investigated on red macroalga Palmaria palmata cultivated for 21 days. The data were combined with the effect of NaNO3 to further investigate the synthesis of these [...] Read more.
The effect of UV radiation on the accumulation of mycosporine-like amino acids (MAAs) and pigments was investigated on red macroalga Palmaria palmata cultivated for 21 days. The data were combined with the effect of NaNO3 to further investigate the synthesis of these nitrogenous compounds. A progressive decrease in both total MAA and pigment contents was observed, with a positive effect of nitrate supply. Usujirene was the only MAA exhibiting a significantly increasing content when exposed to UV radiation, changing from 9% to 24% of the total MAA’s contribution, with no variation observed with NaNO3. This suggests a specific induction or synthesis pathway of usujirene for photoprotection, while the synthesis of other MAAs could have been limited by an insufficient amount of UV radiation and/or irradiance. The photoprotective ability of some MAAs could have been impacted by nitrogen starvation over time, resulting in a limited synthesis and/or potential use of MAAs as a nitrogen source for red macroalgae. The data confirmed the multiple effects of environmental factors on the synthesis of MAAs while providing new insights into the specific synthesis of usujirene, which could find an application in the cosmetics sector as natural sunscreen or an anti-ageing agent. Full article
(This article belongs to the Special Issue Antiphotoaging and Photoprotective Compounds from Marine Environments)
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14 pages, 2502 KiB  
Article
Production of Alginate Oligosaccharides (AOSs) Using Enhanced Physicochemical Properties of Immobilized Alginate Lyase for Industrial Application
by Simranjeet Kaur, Reinu E. Abraham, Christopher M. M. Franco and Munish Puri
Mar. Drugs 2024, 22(3), 120; https://doi.org/10.3390/md22030120 - 04 Mar 2024
Viewed by 1223
Abstract
Alginate lyase (AL) is a polysaccharide-degrading enzyme that can degrade alginate by hydrolyzing glycosidic bonds and produces unsaturated alginate oligosaccharides (AOSs). These AOSs have wide therapeutic and nutraceutical applications. However, to produce alginate oligosaccharides in a cost-effective manner is challenging due to the [...] Read more.
Alginate lyase (AL) is a polysaccharide-degrading enzyme that can degrade alginate by hydrolyzing glycosidic bonds and produces unsaturated alginate oligosaccharides (AOSs). These AOSs have wide therapeutic and nutraceutical applications. However, to produce alginate oligosaccharides in a cost-effective manner is challenging due to the low availability and high cost of this degrading enzyme. Immobilization of the enzyme facilitates industrial applications owing to its stability, reusability, and cost-effectiveness. This study was focused on the enhancement of the properties of alginate lyase and improvement of the production of AOS. Alginate lyase was immobilized on magnetic nanoparticles (NPs) using glutaraldehyde as the crosslinker. The study showed that the maximum binding achieved between NPs and protein in the enzyme was 71% at a ratio of 1:150 NP:protein. As a result of immobilization, the optimum activity of free enzyme which was obtained at 37 °C and pH 7.4 changed to 45 °C and pH 9. Furthermore, the enzyme was thermostable at 45 °C for 3 h with up to 50% reusability for six consecutive cycles. Storage stability after 15 days showed ~67% relative hydrolysis of alginate. The free alginate lyase (25 IU) showed 76% raw biomass (seaweed) hydrolysis which is higher compared to 63% provided by the immobilized enzyme. As a result of efficient hydrolysis, AOSs with molecular weight profile of 370–1040 kDa were produced and detected using HPLC. Full article
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25 pages, 1714 KiB  
Article
Targeted Metabolite Fingerprints of Thirteen Gambierdiscus, Five Coolia and Two Fukuyoa Species
by J. Sam Murray, Emillie M. F. Passfield, Lesley L. Rhodes, Jonathan Puddick, Sarah C. Finch, Kirsty F. Smith, Roel van Ginkel, Elizabeth M. Mudge, Tomohiro Nishimura, Hiroshi Funaki, Masao Adachi, Michèle R. Prinsep and D. Tim Harwood
Mar. Drugs 2024, 22(3), 119; https://doi.org/10.3390/md22030119 - 02 Mar 2024
Viewed by 2444
Abstract
The genus Gambierdiscus produces an array of bioactive hydrophilic and lipophilic secondary metabolites that range in mode of action and toxicity. In this study, the metabolite fingerprint was mapped for thirteen Gambierdiscus, five Coolia and two Fukuyoa species (34 isolates) by assessing [...] Read more.
The genus Gambierdiscus produces an array of bioactive hydrophilic and lipophilic secondary metabolites that range in mode of action and toxicity. In this study, the metabolite fingerprint was mapped for thirteen Gambierdiscus, five Coolia and two Fukuyoa species (34 isolates) by assessing the production of 56 characterised secondary metabolites. Gambierdiscus polynesiensis was the only species to produce Pacific-ciguatoxin-3B (P-CTX3B), P-CTX3C, iso-P-CTX3B/C, P-CTX4A, P-CTX4B and iso-P-CTX4A/B. G. australes produced maitotoxin-1 (MTX-1) and MTX-5, G. cheloniae produced MTX-6 and G. honu produced MTX-7. Ubiquitous production of 44-methylgambierone was observed amongst all the Gambierdiscus isolates, with nine species also producing gambierone. Additional gambierone analogues, including anhydrogambierone (tentatively described herein), were also detected in all Gambierdiscus species, two Coolia and two Fukuyoa species. Gambieroxide was detected in G. lewisii and G. pacificus and gambieric acid A was detected in ten Gambierdiscus species, with G. australes (CAWD381) being the only isolate to produce gambieric acids A–D. This study has demonstrated that the isolates tested to date produce the known CTXs or MTXs, but not both, and highlighted several species that produced ‘unknown’ compounds displaying characteristics of cyclic polyethers, which will be the focus of future compound discovery efforts. Full article
(This article belongs to the Section Marine Toxins)
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20 pages, 4277 KiB  
Article
Using Constellation Pharmacology to Characterize a Novel α-Conotoxin from Conus ateralbus
by Jorge L. B. Neves, Cristoval Urcino, Kevin Chase, Cheryl Dowell, Arik J. Hone, David Morgenstern, Victor M. Chua, Iris Bea L. Ramiro, Julita S. Imperial, Lee S. Leavitt, Jasmine Phan, Fernando A. Fisher, Maren Watkins, Shrinivasan Raghuraman, Jortan O. Tun, Beatrix M. Ueberheide, J. Michael McIntosh, Vitor Vasconcelos, Baldomero M. Olivera and Joanna Gajewiak
Mar. Drugs 2024, 22(3), 118; https://doi.org/10.3390/md22030118 - 29 Feb 2024
Viewed by 1532
Abstract
The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function [...] Read more.
The venom of cone snails has been proven to be a rich source of bioactive peptides that target a variety of ion channels and receptors. α-Conotoxins (αCtx) interact with nicotinic acetylcholine receptors (nAChRs) and are powerful tools for investigating the structure and function of the various nAChR subtypes. By studying how conotoxins interact with nAChRs, we can improve our understanding of these receptors, leading to new insights into neurological diseases associated with nAChRs. Here, we describe the discovery and characterization of a novel conotoxin from Conus ateralbus, αCtx-AtIA, which has an amino acid sequence homologous to the well-described αCtx-PeIA, but with a different selectivity profile towards nAChRs. We tested the synthetic αCtx-AtIA using the calcium imaging-based Constellation Pharmacology assay on mouse DRG neurons and found that αCtx-AtIA significantly inhibited ACh-induced calcium influx in the presence of an α7 positive allosteric modulator, PNU-120596 (PNU). However, αCtx-AtIA did not display any activity in the absence of PNU. These findings were further validated using two-electrode voltage clamp electrophysiology performed on oocytes overexpressing mouse α3β4, α6/α3β4 and α7 nAChRs subtypes. We observed that αCtx-AtIA displayed no or low potency in blocking α3β4 and α6/α3β4 receptors, respectively, but improved potency and selectivity to block α7 nAChRs when compared with αCtx-PeIA. Through the synthesis of two additional analogs of αCtx-AtIA and subsequent characterization using Constellation Pharmacology, we were able to identify residue Trp18 as a major contributor to the activity of the peptide. Full article
(This article belongs to the Section Marine Toxins)
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12 pages, 1432 KiB  
Article
New Phenol Derivatives from the Haima Cold Seep-Derived Fungus Aspergillus subversicolor CYH-17
by Yi-Hao Che, Wen-Ping Ding, Zhi-Hui Xiao, Jia-Min Wu, Hao Yin, Fa-Zuo Wang and Si Zhang
Mar. Drugs 2024, 22(3), 117; https://doi.org/10.3390/md22030117 - 29 Feb 2024
Viewed by 1045
Abstract
Seven new phenol derivatives, subversins A–E (15), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (913) were isolated [...] Read more.
Seven new phenol derivatives, subversins A–E (15), subversic acid A (6) and epi-wortmannine G (7); one new natural product, 4-hydroxy-7-methoxyphthalide (8); and five known compounds (913) were isolated from the fungus Aspergillus subversicolor CYH-17 collected from the Haima cold seep. The structures and absolute configurations of these compounds were determined via NMR, MS, optical rotation, electronic circular dichroism (ECD) calculation, X-ray diffraction analysis and comparison with the literature. Compounds 2 and 5 were two pairs of enantiomers. All compounds were tested for their α-glucosidase and acetylcholinesterase (AChE) inhibitory activity, antioxidant activity and antibacterial activity, but no obvious activity was observed among these studied compounds. Full article
(This article belongs to the Special Issue Bioactive Secondary Metabolites of Marine Fungi 2.0)
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19 pages, 889 KiB  
Article
New Forms of Neuroactive Phospholipids for DHA Enrichment in Brain
by Romina Gomes, Inês Mendes, Maria Paula Duarte, Narcisa M. Bandarra and Ana Gomes-Bispo
Mar. Drugs 2024, 22(3), 116; https://doi.org/10.3390/md22030116 - 29 Feb 2024
Viewed by 1264
Abstract
Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer’s disease (AD). After ingestion, dietary DHA must cross the blood–brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA [...] Read more.
Low levels of docosahexaenoic acid (DHA) in the brain have been related to neurological disorders, like Alzheimer’s disease (AD). After ingestion, dietary DHA must cross the blood–brain barrier, where it is absorbed as lysophosphatidylcholine (LPC), due to its role as a preferential DHA carrier in the brain. This work aimed at the production of LPC-DHA extracts to be used in supplementation/food fortification intended neural enrichment in DHA. As it is rich in DHA, especially its phospholipids (PL), Atlantic mackerel (Scomber scombrus, caught in Spring/2022) was used as a raw material. The polar lipids fraction was separated and hydrolysed with Rhizomucor miehei lipase, to enzymatically convert phosphatidylcholine (PC) into LPC. The fish (muscle and by-products) lipids fraction was used for total lipids (TL) content, lipid classes (LC) and fatty acid (FA) profile evaluation, whilst polar lipids extracts were studied for LC production and FA analysis. Muscle TL ranged between 1.45 and 4.64 g/100 g (WW), while by-products accounted for 7.56-8.96 g/100 g, with the highest contents being found in March. However, PL were more abundant in muscle (22.46–32.20% of TL). For polar lipids extracts, PL represented 50.79% of TL, among which PC corresponded to 57.76% and phosphatidylethanolamine to 42.24%. After hydrolysis, nearly half of this PC was converted into LPC. When compared to the initial PC, DHA relative content (33.6% of total FA) was significantly higher after hydrolysis: 55.6% in PC and 73.6% in LPC. Such extract, obtained from this undervalued species, may represent a promising strategy to increase DHA uptake into brain cells while allowing this species to upgrade. Full article
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13 pages, 1454 KiB  
Article
Jasmonates and Ethylene Shape Floridoside Synthesis during Carposporogenesis in the Red Seaweed Grateloupia imbricata
by Pilar Garcia-Jimenez, Diana del Rosario-Santana and Rafael R. Robaina
Mar. Drugs 2024, 22(3), 115; https://doi.org/10.3390/md22030115 - 28 Feb 2024
Viewed by 1082
Abstract
Floridoside is a galactosyl–glycerol compound that acts to supply UDP-galactose and functions as an organic osmolyte in response to salinity in Rhodophyta. Significantly, the UDP-galactose pool is shared for sulfated cell wall galactan synthesis, and, in turn, affected by thallus development alongside carposporogenesis [...] Read more.
Floridoside is a galactosyl–glycerol compound that acts to supply UDP-galactose and functions as an organic osmolyte in response to salinity in Rhodophyta. Significantly, the UDP-galactose pool is shared for sulfated cell wall galactan synthesis, and, in turn, affected by thallus development alongside carposporogenesis induced by volatile growth regulators, such as ethylene and methyl jasmonate, in the red seaweed Grateloupia imbricata. In this study, we monitored changes in the floridoside reservoir through gene expression controlling both the galactose pool and glyceride pool under different reproductive stages of G. imbricata and we considered changing salinity conditions. Floridoside synthesis was followed by expression analysis of galactose-1-phosphate uridyltransferase (GALT) as UDP-galactose is obtained from UDP-glucose and glucose-1P, and through α-galactosidase gene expression as degradation of floridoside occurs through the cleavage of galactosyl residues. Meanwhile, glycerol 3-phosphate is connected with the galactoglyceride biosynthetic pathway by glycerol 3-phosphate dehydrogenase (G3PD), monogalactosyl diacylglyceride synthase (MGDGS), and digalactosyl diacylglyceride synthase (DGDGS). The results of our study confirm that low GALT transcripts are correlated with thalli softness to locate reproductive structures, as well as constricting the synthesis of UDP-hexoses for galactan backbone synthesis in the presence of two volatile regulators and methionine. Meanwhile, α-galactosidase modulates expression according to cystocarp maturation, and we found high transcripts in late development stages, as occurred in the presence of methyljasmonate, compared to early stages in ethylene. Regarding the acylglyceride pool, the upregulation of G3PD, MGDGS, and DGDGS gene expression in G. imbricata treated with MEJA supports lipid remodeling, as high levels of transcripts for MGDGS and DGDGS provide membrane stability during late development stages of cystocarps. Similar behavior is assumed in three naturally collected thalli development stages—namely, fertile, fertilized, and fertile—under 65 psu salinity conditions. Low transcripts for α-galactosidase and high for G3PD are reported in infertile and fertilized thalli, which is the opposite to high transcripts for α-galactosidase and low for G3PD encountered in fertile thalli within visible cystocarps compared to each of their corresponding stages in 35 psu. No significant changes are reported for MGDGS and DGDGS. It is concluded that cystocarp and thallus development stages affect galactose and glycerides pools with interwoven effects on cell wall polysaccharides. Full article
(This article belongs to the Special Issue Characterization of Bioactive Components in Edible Algae 3rd Edition)
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46 pages, 5370 KiB  
Review
Marine-Derived Anticancer Agents Targeting Apoptotic Pathways: Exploring the Depths for Novel Cancer Therapies
by Doralyn S. Dalisay, Chuckcris P. Tenebro, Edna M. Sabido, Angelica Faith L. Suarez, Melissa June V. Paderog, Rikka Reyes-Salarda and Jonel P. Saludes
Mar. Drugs 2024, 22(3), 114; https://doi.org/10.3390/md22030114 - 28 Feb 2024
Viewed by 2947
Abstract
Extensive research has been conducted on the isolation and study of bioactive compounds derived from marine sources. Several natural products have demonstrated potential as inducers of apoptosis and are currently under investigation in clinical trials. These marine-derived compounds selectively interact with extrinsic and [...] Read more.
Extensive research has been conducted on the isolation and study of bioactive compounds derived from marine sources. Several natural products have demonstrated potential as inducers of apoptosis and are currently under investigation in clinical trials. These marine-derived compounds selectively interact with extrinsic and intrinsic apoptotic pathways using a variety of molecular mechanisms, resulting in cell shrinkage, chromatin condensation, cytoplasmic blebs, apoptotic bodies, and phagocytosis by adjacent parenchymal cells, neoplastic cells, or macrophages. Numerous marine-derived compounds are currently undergoing rigorous examination for their potential application in cancer therapy. This review examines a total of 21 marine-derived compounds, along with their synthetic derivatives, sourced from marine organisms such as sponges, corals, tunicates, mollusks, ascidians, algae, cyanobacteria, fungi, and actinobacteria. These compounds are currently undergoing preclinical and clinical trials to evaluate their potential as apoptosis inducers for the treatment of different types of cancer. This review further examined the compound’s properties and mode of action, preclinical investigations, clinical trial studies on single or combination therapy, and the prospective development of marine-derived anticancer therapies. Full article
(This article belongs to the Special Issue Discovery of Marine-Derived Anticancer Agents)
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17 pages, 2908 KiB  
Article
Exploring the Potential of Crassostrea nippona Hydrolysates as Dietary Supplements for Mitigating Dexamethasone-Induced Muscle Atrophy in C2C12 Cells
by M. J. M. S. Kurera, D. P. Nagahawatta, N. M. Liyanage, H. H. A. C. K. Jayawardhana, D. S. Dissanayake, Hyo-Geun Lee, Young-Sang Kim, Sang In Kang and You-Jin Jeon
Mar. Drugs 2024, 22(3), 113; https://doi.org/10.3390/md22030113 - 28 Feb 2024
Viewed by 1168
Abstract
Muscle atrophy is a detrimental and injurious condition that leads to reduced skeletal muscle mass and disruption of protein metabolism. Oyster (Crassostrea nippona) is a famous and commonly consumed shellfish in East Asia and has become a popular dietary choice worldwide. [...] Read more.
Muscle atrophy is a detrimental and injurious condition that leads to reduced skeletal muscle mass and disruption of protein metabolism. Oyster (Crassostrea nippona) is a famous and commonly consumed shellfish in East Asia and has become a popular dietary choice worldwide. The current investigation evaluated the efficacy of C. nippona against muscle atrophy, which has become a severe health issue. Mammalian skeletal muscles are primarily responsible for efficient metabolism, energy consumption, and body movements. The proteins that regulate muscle hypertrophy and atrophy are involved in muscle growth. C. nippona extracts were enzymatically hydrolyzed using alcalase (AOH), flavourzyme (FOH), and protamex (POH) to evaluate their efficacy in mitigating dexamethasone-induced muscle damage in C2C12 cells in vitro. AOH exhibited notable cell proliferative abilities, promoting dose-dependent myotube formation. These results were further solidified by protein expression analysis. Western blot and gene expression analysis via RT-qPCR demonstrated that AOH downregulated MuRF-1, Atrogin, Smad 2/3, and Foxo-3a, while upregulating myogenin, MyoD, myosin heavy chain expression, and mTOR, key components of the ubiquitin–proteasome and mTOR signaling pathways. Finally, this study suggests that AOH holds promise for alleviating dexamethasone-induced muscle atrophy in C2C12 cells in vitro, offering insights for developing functional foods targeting conditions akin to sarcopenia. Full article
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22 pages, 2121 KiB  
Article
An Eco-Friendly Extraction and Purification Approach for Obtaining Active Ingredients for Cosmetics from Two Marine Brown Seaweeds
by Leslie Gager, Solène Connan, Stéphane Cérantola, Sylvain Petek, Céline Couteau, Laurence Coiffard and Valérie Stiger-Pouvreau
Mar. Drugs 2024, 22(3), 112; https://doi.org/10.3390/md22030112 - 28 Feb 2024
Viewed by 1151
Abstract
Brown seaweeds are attracting attention due to their richness in bioactive compounds, in particular, their phlorotannins. We present here a case study of two Fucales, Ascophyllum nodosum and Halidrys siliquosa, sustainably collected, to produce active polyphenols for the cosmetics sector. Phenolic contents of [...] Read more.
Brown seaweeds are attracting attention due to their richness in bioactive compounds, in particular, their phlorotannins. We present here a case study of two Fucales, Ascophyllum nodosum and Halidrys siliquosa, sustainably collected, to produce active polyphenols for the cosmetics sector. Phenolic contents of crude extracts, obtained by Accelerated Solvent Extraction (ASE), were more elevated in H. siliquosa at 100.05 mg/g dry weight (DW) than in A. nodosum (29.51 mg/g DW), considering 3 cycles with cell inversion. The temperature of extraction for a high phenolic content and high associated antioxidant activities close to positive controls was 150 °C for both algae and the use of only one cycle was enough. A semi-purification process using Solid-phase Extraction (SPE) was carried out on both ASE crude extracts (one per species). The majority of phlorotannins were found in the ethanolic SPE fraction for A. nodosum and the hydroethanolic one for H. siliquosa. The SPE process allowed us to obtain more concentrated fractions of active phenolic compounds (×1.8 and 2 in A. nodosum and H. siliquosa, respectively). Results are discussed in regard to the exploitation of seaweeds in Brittany and to the research of sustainable processes to produce active natural ingredients for cosmetics. Full article
(This article belongs to the Special Issue Discoveries of Bioactive Compounds from Algae)
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16 pages, 3462 KiB  
Article
Synthesis and Hypoglycemic Effect of Insulin from the Venom of Sea Anemone Exaiptasia diaphana
by Qiqi Guo, Tianle Tang, Jingyue Lu, Meiling Huang, Junqing Zhang, Linlin Ma and Bingmiao Gao
Mar. Drugs 2024, 22(3), 111; https://doi.org/10.3390/md22030111 - 27 Feb 2024
Viewed by 1032
Abstract
Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five [...] Read more.
Sea anemone venom, abundant in protein and peptide toxins, serves primarily for predatory defense and competition. This study delves into the insulin-like peptides (ILPs) present in sea anemones, particularly focusing on their role in potentially inducing hypoglycemic shock in prey. We identified five distinct ILPs in Exaiptasia diaphana, exhibiting varied sequences. Among these, ILP-Ap04 was successfully synthesized using solid phase peptide synthesis (SPPS) to evaluate its hypoglycemic activity. When tested in zebrafish, ILP-Ap04 significantly reduced blood glucose levels in a model of diabetes induced by streptozotocin (STZ) and glucose, concurrently affecting the normal locomotor behavior of zebrafish larvae. Furthermore, molecular docking studies revealed ILP-Ap04’s unique interaction with the human insulin receptor, characterized by a detailed hydrogen-bonding network, which supports a unique mechanism for its hypoglycemic effects. Our findings suggest that sea anemones have evolved sophisticated strategies to activate insulin receptors in vertebrates, providing innovative insights into the design of novel drugs for the treatment of diabetes. Full article
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12 pages, 3141 KiB  
Article
Rational Design of Potent α-Conotoxin PeIA Analogues with Non-Natural Amino Acids for the Inhibition of Human α9α10 Nicotinic Acetylcholine Receptors
by Tianmiao Li, Han-Shen Tae, Jiazhen Liang, Zixuan Zhang, Xiao Li, Tao Jiang, David J. Adams and Rilei Yu
Mar. Drugs 2024, 22(3), 110; https://doi.org/10.3390/md22030110 - 27 Feb 2024
Viewed by 962
Abstract
α-Conotoxins (α-CTxs) are structurally related peptides that antagonize nicotinic acetylcholine receptors (nAChRs), which may serve as new alternatives to opioid-based treatment for pain-related conditions. The non-natural amino acid analogues of α-CTxs have been demonstrated with improved potency compared to the native peptide. In [...] Read more.
α-Conotoxins (α-CTxs) are structurally related peptides that antagonize nicotinic acetylcholine receptors (nAChRs), which may serve as new alternatives to opioid-based treatment for pain-related conditions. The non-natural amino acid analogues of α-CTxs have been demonstrated with improved potency compared to the native peptide. In this study, we chemically synthesized Dab/Dap-substituted analogues of α-CTx PeIA and evaluated their activity at heterologously expressed human α9α10 nAChRs. PeIA[S4Dap, S9Dap] had the most potent half-maximal inhibitory concentration (IC50) of 0.93 nM. Molecular dynamic simulations suggested that the side chain amino group of Dap4 formed additional hydrogen bonds with S168 and D169 of the receptor and Dap9 formed an extra hydrogen bond interaction with Q34, which is distinctive to PeIA. Overall, our findings provide new insights into further development of more potent analogues of α-CTxs, and PeIA[S4Dap, S9Dap] has potential as a drug candidate for the treatment of chronic neuropathic pain. Full article
(This article belongs to the Section Marine Toxins)
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