Marine Drugs

15 pages, 3882 KiB

Open AccessArticle

Structural Characterization and Anticoagulant Potential of Colochirus quadrangularis Fucosylated Glycosaminoglycan 5−12 Oligomers with Unusual Branches

by Xuedong Zhang, Guangwei Yan, Xinming Liu, Jiewen Fu, Xiang Shi, Pei Cao, Yuqian Sun, Shengping Zhong, Jiale Nong, Peiqi Jiang, Yonghong Liu, Baoshun Zhang, Qingxia Yuan and Longyan Zhao

Mar. Drugs 2025, 23(2), 64; https://doi.org/10.3390/md23020064 (registering DOI) - 1 Feb 2025

Abstract

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products [...] Read more.

The depolymerized products and oligosaccharide fractions from sea cucumber fucosylated glycosaminoglycans (FGs) are promising anticoagulant candidates, and more novel FG-derived oligosaccharides from low-priced sea cucumbers are expected to be obtained. This study isolated 5−12 oligomers (OF1−OF3) with unusual branches from β-eliminative depolymerized products of Colochirus quadrangularis FG (CqFG). Detailed NMR analyses showed that OF1−OF3 consisted of a chondroitin 4,6-sulfates backbone and some sulfated fucosyl branches (FucS), including monosaccharides (α-l-Fuc_2S4S, α-l-Fuc_3S, α-l-Fuc_4S, α-l-Fuc_2S3S4S, and α-l-Fuc_2S) and a disaccharide D-Gal_3S4S-α1,3-l-Fuc_2S4S with the ratio of ~36:35:10:7:3:9, attached to the C-3 position of β-d-GlcA or its derivatives, such as α-l-Δ4,5GlcA and β-d-GlcA-ol. Unusually, α-l-Fuc_3S was the main FucS branch; no α-l-Fuc_3S4S branch was found, and α-l-Fuc_2S3S4S and α-l-Fuc_2S branches were also found in OF1–OF3. The OF2 and OF3 could strongly inhibit the intrinsic and common coagulation pathways. Intrinsic FXase is a target of OF2 and OF3 inhibiting the intrinsic coagulation pathways, and the unusual side chains may increase the intrinsic FXase inhibitory activity. OF2 and OF3 showed negligible bleeding risk, and less bleeding than heparin (HP), low-molecular-weight heparins (LMWHs), and CqFG. These findings support novel FG oligosaccharides with some unusual branches from low-priced sea cucumbers to be prepared as safer anticoagulants. Full article

(This article belongs to the Special Issue Marine Sulfated Glycans)

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22 pages, 8432 KiB

Open AccessArticle

Antioxidant Peptides from Miiuy Croaker Swim Bladders: Ameliorating Effect and Mechanism in NAFLD Cell Model through Regulation of Hypolipidemic and Antioxidant Capacity

by Yu-Mei Wang, Ming-Xue Ge, Su-Zhen Ran, Xin Pan, Chang-Feng Chi and Bin Wang

Mar. Drugs 2025, 23(2), 63; https://doi.org/10.3390/md23020063 (registering DOI) - 1 Feb 2025

Abstract

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and [...] Read more.

In this work, the hypolipidemic and antioxidative capacity of FSGLR (S7) and GIEWA (S10) from miiuy croaker swim bladders was explored systematically in an oleic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model of HepG2 cells. Moreover, the hypolipidemic activity of S7 and S10 and their antioxidative abilities were preliminarily investigated in combination with molecular docking technology. The results indicated that S7 and S10 could decrease the amount of lipid accumulation and the content of triglycerides (TG) and total cholesterol (TC) in the OA-induced NAFLD cell model in a dose-dependent manner. In addition, S7 and S10 exhibited better bile salt binding, pancreatic lipase (PL) inhibition, and cholesterol esterase (CE) inhibition capacities. The hypolipidemic mechanisms of S7 and S10 were connected with the downregulation of the mRNA expression levels of adipogenic factors, including sterol-regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), sterol-regulatory element-binding protein (SREBP)-2, hydroxymethylglutaryl-CoA reductase (HMGR), and fatty acid synthase (FAS) (p < 0.01), and the upregulation of the mRNA expression of β-oxidation-related factors, including carnitine palmitoyltransferase 1 (CPT-1), acyl-CoA oxidase 1 (ACOX-1), and peroxisome proliferator-activated receptor α (PPARα). Moreover, FSGLR (S7) and GIEWA (S10) could significantly protect HepG2 cells against OA-induced oxidative damage, and their antioxidant mechanisms were related to the increased activity of intracellular antioxidant proteases (superoxide dismutase, SOD; glutathione peroxidase, GSH-PX; catalase, CAT) to remove excess reactive oxygen species (ROS) and decrease the production of malondialdehyde (MDA). The presented findings indicate that the hypolipidemic and antioxidant functions and mechanisms of S7 and S10 could make them potential hypolipidemic and antioxidant candidates for the treatment of NAFLD. Full article

(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)

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23 pages, 1060 KiB

Open AccessReview

Distribution, Biosynthesis, and Function of Carotenoids in Oxygenic Phototrophic Algae

by Shinichi Takaichi

Mar. Drugs 2025, 23(2), 62; https://doi.org/10.3390/md23020062 - 31 Jan 2025

Abstract

For photosynthesis, oxygenic phototrophic organisms necessarily contain not only chlorophylls but also carotenoids. Various carotenoids have been identified in algae and taxonomic studies of algae have been conducted. In this review, the relationship between the distribution of chlorophylls and carotenoids and the phylogeny [...] Read more.

For photosynthesis, oxygenic phototrophic organisms necessarily contain not only chlorophylls but also carotenoids. Various carotenoids have been identified in algae and taxonomic studies of algae have been conducted. In this review, the relationship between the distribution of chlorophylls and carotenoids and the phylogeny of sea and freshwater oxygenic phototrophs, including cyanobacteria, red algae, brown algae, and green algae, is summarized. These phototrophs contain division- or class-specific chlorophylls and carotenoids, such as fucoxanthin, peridinin, diadinoxanthin, and siphonaxanthin. The distribution of β-carotene and its derivatives, including β-carotene, zeaxanthin, violaxanthin, neoxanthin, diadinoxanthin, fucoxanthin, and peridinin (β-branch carotenoids), are limited to divisions of a part of Rhodophyta, Cryptophyta, Heterokontophyta, Haptophyta, and Dinophyta. Meanwhile, the distribution of α-carotene and its derivatives, such as lutein, loroxanthin, and siphonaxanthin (α-branch carotenoids), are limited to divisions of a part of Rhodophyta (macrophytic type), Cryptophyta, Euglenophyta, Chlorarachniophyta, and Chlorophyta. In addition, carotenogenesis pathways are also discussed based on the chemical structures of carotenoids and the known characteristics of carotenogenesis enzymes in other organisms. The specific genes and enzymes for carotenogenesis in algae are not yet known. Most carotenoids bind to membrane-bound pigment-protein complexes, such as reaction centers and light-harvesting complexes. Some carotenoids function in photosynthesis and are briefly summarized. Water-soluble peridinin-chlorophyll a-protein (PCP) and orange carotenoid protein (OCP) have also been characterized. This review is a summary and update from the previous review on the distribution of major carotenoids, primary carotenogenesis pathways, and the characteristics of carotenogenesis enzymes and genes. Full article

(This article belongs to the Special Issue Recent Advances in Marine-Derived Pigments)

38 pages, 2463 KiB

Open AccessReview

The Toxic Effects of Environmental Domoic Acid Exposure on Humans and Marine Wildlife

by Ami E. Krasner, Margaret E. Martinez, Cara L. Field and Spencer E. Fire

Mar. Drugs 2025, 23(2), 61; https://doi.org/10.3390/md23020061 - 29 Jan 2025

Abstract

Biotoxins produced by harmful algal blooms (HABs) are a substantial global threat to ocean and human health. Domoic acid (DA) is one such biotoxin whose negative impacts are forecasted to increase with climate change and coastal development. This manuscript serves as a review [...] Read more.

Biotoxins produced by harmful algal blooms (HABs) are a substantial global threat to ocean and human health. Domoic acid (DA) is one such biotoxin whose negative impacts are forecasted to increase with climate change and coastal development. This manuscript serves as a review of DA toxicosis after environmental exposure in humans and wildlife, including an introduction to HAB toxins, the history of DA toxicosis, DA production, toxicokinetic properties of DA, susceptibility, clinical signs, DA detection methods and other diagnostic tests, time course of toxicosis, treatment, prognostics, and recommendations for future research. Additionally, we highlight the utility of California sea lions (CSLs; Zalophus californianus) as a model and sentinel of environmental DA exposure. Full article

(This article belongs to the Special Issue Commemorating the Launch of the Section "Marine Toxins")

35 pages, 1644 KiB

Open AccessReview

Marine-Derived Polysaccharides and Their Potential Health Benefits in Nutraceutical Applications

by Joana Carrasqueira, Susana Bernardino, Raul Bernardino and Clélia Afonso

Mar. Drugs 2025, 23(2), 60; https://doi.org/10.3390/md23020060 - 28 Jan 2025

Abstract

Marine-derived polysaccharides have sparked immense interest in the nutraceutical industry as they possess a wide range of bioactivities which are highlighted in this review. These include antioxidants, anti-inflammatory, anti-cancer, gut microbiota regulator, anti-diabetic, and anti-obesity. Algae, marine invertebrates, vertebrates, and microorganisms are the [...] Read more.

Marine-derived polysaccharides have sparked immense interest in the nutraceutical industry as they possess a wide range of bioactivities which are highlighted in this review. These include antioxidants, anti-inflammatory, anti-cancer, gut microbiota regulator, anti-diabetic, and anti-obesity. Algae, marine invertebrates, vertebrates, and microorganisms are the main sources of marine polysaccharides, such as alginate, fucoidan, laminarin, carrageenan, chitosan, glycosaminoglycans, and exopolysaccharides. The structure and functional groups of these compounds influence their bioactive properties. Moreover, the functional properties of polysaccharides, such as gelling, thickening, and stabilising capabilities, are also crucial in product development, where they can serve as gluten substitutes in bakery goods and stabilisers in icings, sauces, and yoghurts. The potential of commercial products under development, such as marine polysaccharide supplements, is discussed, along with already commercialised products in the nutraceutical market. This review emphasises the enormous potential of marine-derived polysaccharides as bioactive compounds with health benefits and commercial value. Full article

(This article belongs to the Special Issue Polysaccharides from Marine Environment)

17 pages, 4405 KiB

Open AccessArticle

Chemical Characterization of Bioactive Compounds in Extracts and Fractions from Litopenaeus vannamei Muscle

by Sandra Carolina De La Reé-Rodríguez, María Jesús González, Ingrid Fernández, José Luis Garrido, Erika Silva-Campa, Norma Violeta Parra-Vergara, Carmen María López-Saiz and Isabel Medina

Mar. Drugs 2025, 23(2), 59; https://doi.org/10.3390/md23020059 - 27 Jan 2025

Abstract

Marine organisms are a vital source of biologically active compounds. Organic extracts from the muscle of the Pacific white shrimp (L. vannamei) have shown antiproliferative effects on tumor cells, including breast adenocarcinoma. This study aimed to analyze these extracts’ composition and [...] Read more.

Marine organisms are a vital source of biologically active compounds. Organic extracts from the muscle of the Pacific white shrimp (L. vannamei) have shown antiproliferative effects on tumor cells, including breast adenocarcinoma. This study aimed to analyze these extracts’ composition and confirm their specificity for breast adenocarcinoma cells without harming normal cells. An organic chloroform extract from L. vannamei muscle was divided using a solvent partition procedure with methanol and hexane. The methanolic partition was fractionated through an open preparative liquid chromatography column to isolate compounds with biological activity, that were later tested on MDA-MB-231 (breast adenocarcinoma), and recently tested on MCF10-A (non-cancerous breast epithelial cells). Cells incubated with these fractions were assessed for viability and morphological changes using fluorescence confocal microscopy. Fractions F#13 and F#14 reduced MDA-MB-231 cancer cell viability at 100 µg/mL without affecting non-cancerous MCF-10A cells, inducing apoptosis-related changes in cancer cells. These fractions contained EPA and DHA free fatty acids, specifically F#13 contained free and esterified astaxanthin as well. The high levels of free linoleic acid 18:2 ω-6, EPA, and DHA (in a 2:1 ratio, EPA:DHA), along with free and esterified astaxanthin in F#13, significantly reduced breast adenocarcinoma cell viability, nearly to that achieved by cisplatin, a chemotherapy drug. Full article

(This article belongs to the Special Issue Sustainable Valorization of Seafood By-Products through Recovery of Valuable Bioactive Compounds 2nd Edition)

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18 pages, 1384 KiB

Open AccessArticle

Exploring Phaeodactylum tricornutum for Nutraceuticals: Cultivation Techniques and Neurotoxin Risk Assessment

by Tobias Ebbing, Lena Kopp, Konstantin Frick, Tabea Simon, Berit Würtz, Jens Pfannstiel, Ulrike Schmid-Staiger, Stephan C. Bischoff and Günter E. M. Tovar

Mar. Drugs 2025, 23(2), 58; https://doi.org/10.3390/md23020058 - 26 Jan 2025

Abstract

This study investigates the potential of the diatom Phaeodactylum tricornutum (PT) as a sustainable and nutritionally valuable food source, focusing on its ability to produce bioactive compounds such as eicosapentaenoic acid, fucoxanthin, chrysolaminarin (CRY) and proteins. PT was cultivated in a flat-plate airlift [...] Read more.

This study investigates the potential of the diatom Phaeodactylum tricornutum (PT) as a sustainable and nutritionally valuable food source, focusing on its ability to produce bioactive compounds such as eicosapentaenoic acid, fucoxanthin, chrysolaminarin (CRY) and proteins. PT was cultivated in a flat-plate airlift photobioreactor (FPA-PBR) illuminated with LEDs from two sides. The study aimed to monitor and minimize β-methylamino-L-alanine (BMAA) levels to address safety concerns. The data showed that the selected FPA-PBR setup was superior in biomass and EPA productivity, and CRY production was reduced. No BMAA was detected in any biomass sample during cultivation. By adjusting the cultivation conditions, PT biomass with different compositional profiles could be produced, enabling various applications in the food and health industries. Biomass from nutrient-repleted conditions is rich in EPA and Fx, with nutritional and health benefits. Biomass from nutrient-depleted conditions accumulated CRY, which can be used as dietary fiber. These results highlight the potential of PT as a versatile ingredient for human consumption and the effectiveness of FPA-PBRs with artificial lighting in producing high-quality biomass. This study also provides the basis for future research to optimize photobioreactor conditions to increase production efficiency and to tailor the biomass profiles of PT for targeted health-promoting applications. Full article

(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products, 2nd Edition)

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15 pages, 1727 KiB

Open AccessArticle

Characterizing the Ultraviolet (UV) Screening Ability of L-5-Sulfanylhistidine Derivatives on Human Dermal Fibroblasts

by Alessia Luccarini, Fabio Marcheggiani, Roberta Galeazzi, Annalisa Zuccarotto, Immacolata Castellano and Elisabetta Damiani

Mar. Drugs 2025, 23(2), 57; https://doi.org/10.3390/md23020057 - 24 Jan 2025

Abstract

Using sunscreens is one of the most widespread measures to protect human skin from sun ultraviolet radiation (UVR) damage. However, several studies have highlighted the toxicity of certain inorganic and organic UV filters used in sunscreens for the marine environment and human health. [...] Read more.

Using sunscreens is one of the most widespread measures to protect human skin from sun ultraviolet radiation (UVR) damage. However, several studies have highlighted the toxicity of certain inorganic and organic UV filters used in sunscreens for the marine environment and human health. An alternative strategy may involve the use of natural products of marine origin to counteract UVR-mediated damage. Ovothiols are sulfur-containing amino acids produced by marine invertebrates, microalgae, and bacteria, endowed with unique antioxidant and UV-absorption properties. This study aimed to evaluate the protective effect of synthetic L-5-sulfanyl histidine derivatives, inspired by natural ovothiols, on human dermal fibroblasts (HDFs) upon UVA exposure. By using a custom-made experimental set-up to assess the UV screening ability, we measured the levels of cytosolic and mitochondrial reactive oxygen species (ROS), as well as cell viability and apoptosis in HDFs, in the presence of tested compounds, after UVA exposure, using flow cytometry assays with specific fluorescent probes. The results show that L-5-sulfanyl histidine derivatives display a UV screening capacity and prevent loss in cell viability, the production of cytosolic and mitochondrial ROS induced by UVA exposure in HDFs, and subsequent apoptosis. Overall, this study sheds light on the potential applications of marine-inspired sulfur-containing amino acids in developing alternative eco-safe sunscreens for UVR skin protection. Full article

(This article belongs to the Special Issue Marine Bioactive Compounds for Skin Health)

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28 pages, 3458 KiB

Open AccessReview

Ulva Seaweed-Derived Ulvan: A Promising Marine Polysaccharide as a Sustainable Resource for Biomaterial Design

by Rizfi Fariz Pari, Uju Uju, Safrina Dyah Hardiningtyas, Wahyu Ramadhan, Rie Wakabayashi, Masahiro Goto and Noriho Kamiya

Mar. Drugs 2025, 23(2), 56; https://doi.org/10.3390/md23020056 - 24 Jan 2025

Abstract

Green seaweed is currently underused compared with other major seaweed types. Many scientists have reported applications of the green seaweed Ulva in various fields in recent years, which makes it a candidate for biomass production in industrial biorefineries. Ulva contains a unique polysaccharide [...] Read more.

Green seaweed is currently underused compared with other major seaweed types. Many scientists have reported applications of the green seaweed Ulva in various fields in recent years, which makes it a candidate for biomass production in industrial biorefineries. Ulva contains a unique polysaccharide called ulvan, which is being considered for medicinal and pharmacological applications. Ulvan is a sulfated polysaccharide including rhamnose and glucuronic acid residues, which has a range of bioactivities, including immunomodulatory, antimicrobial, and anticoagulant properties. The biocompatibility of ulvan makes it a versatile candidate for biomaterial design. This review presents an in-depth analysis of the potential applications of ulvan, starting with extraction methods and structural/biological characterization and moving on to biomaterial design. We also highlight the advantages of ulvan over traditional seaweed polysaccharides such as agar, carrageenan, and alginate. Full article

(This article belongs to the Special Issue Marine Polysaccharide-Based Biomaterials)

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15 pages, 1814 KiB

Open AccessReview

Components and Biological Activities of Venom from Lionfishes (Scorpaenidae: Pterois)

by Candelario Rodriguez, Jafeth Carrasco, Gaspar Bruner-Montero, Osmindo Rodrigues Pires Júnior, Marcelino Gutiérrez and Edgardo Díaz-Ferguson

Mar. Drugs 2025, 23(2), 55; https://doi.org/10.3390/md23020055 - 23 Jan 2025

Abstract

Fishes of the genus Pterois possess spines that provoke intense pain, which can last for weeks. Since the first toxicological description of their spine venom, a significant amount of research has been published regarding their biochemical characterization. This minireview presents research published from [...] Read more.

Fishes of the genus Pterois possess spines that provoke intense pain, which can last for weeks. Since the first toxicological description of their spine venom, a significant amount of research has been published regarding their biochemical characterization. This minireview presents research published from 1959 to 2024 on bioactive substances found in Pterois species. Pterois venom mainly contains peptides and proteins that display a range of biological activities, including anticancer, antimicrobial, antioxidant, antiviral, enzymatic, cardiovascular, procoagulant, neurological, neuromuscular, and nutraceutical effects. Although Pterois venom contains bioactive substances, the toxic side effects, such as hemolysis and nociception, of these venoms should be considered. Hence, further intense research is needed to establish the potential uses of Pterois venom for human health. Full article

(This article belongs to the Special Issue Marine Toxins: Characterization, Detection, Classification and Potential Therapeutics)

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17 pages, 9218 KiB

Open AccessArticle

Blockade of the STAT3/BCL-xL Axis Leads to the Cytotoxic and Cisplatin-Sensitizing Effects of Fucoxanthin, a Marine-Derived Carotenoid, on Human Bladder Urothelial Carcinoma Cells

by Wen-Chyi Dai, Tzu-Hsuan Chen, Tzu-Ching Peng, Yung-Ching He, Chao-Yu Hsu and Chia-Che Chang

Mar. Drugs 2025, 23(2), 54; https://doi.org/10.3390/md23020054 - 22 Jan 2025

Abstract

Bladder cancer is a globally prevalent urological malignancy, with transitional carcinoma (TCC) representing the majority of cases. Cisplatin is the primary drug for metastatic bladder cancer chemotherapy; however, its application is limited by nephrotoxicity and resistance. Signal Transducer and Activator of Transcription 3 [...] Read more.

Bladder cancer is a globally prevalent urological malignancy, with transitional carcinoma (TCC) representing the majority of cases. Cisplatin is the primary drug for metastatic bladder cancer chemotherapy; however, its application is limited by nephrotoxicity and resistance. Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogenic transcription factor often overactivated in various cancers, making it an appealing drug target. Fucoxanthin, a marine carotenoid, has significant anticancer properties. This study explored Fucoxanthin’s cytotoxic effects and its potential to potentiate the efficacy of Cisplatin, along with the mechanisms underlying these effects, on human bladder TCC cells. We demonstrated that Fucoxanthin is cytotoxic to bladder TCC cells by inducing apoptosis, evidenced by z-VAD-fmk-mediated annulment of Fucoxanthin’s cytotoxicity. Furthermore, Fucoxanthin reduced the levels of inherent or interleukin-6-induced tyrosine 705-phosphorylated STAT3 accompanied by downregulating BCL-xL, a well-established STAT3 target. Notably, ectopic expression of STAT3-C, a dominant-active STAT3 mutant, or BCL-xL thwarted Fucoxanthin’s proapoptotic and cytotoxic actions. Moreover, Fucoxanthin at subtoxic dosages enhanced the susceptibility to Cisplatin-induced apoptosis of bladder TCC cells initially resistant to Cisplatin. Remarkably, this Cisplatin-sensitizing effect of Fucoxanthin was abrogated when cells ectopically expressed STAT3-C or BCL-xL. Overall, for the first time, we proved that the proapoptotic, cytotoxic, and Cisplatin-sensitizing effects of Fucoxanthin on human bladder TCC cells are attributed to the blockade of the STAT3/BCL-xL axis. Our findings highlight that targeting the STAT3/BCL-xL axis is a promising strategy to eliminate bladder TCC cells and facilitate Cisplatin sensitization, and further support the potential of incorporating Fucoxanthin into Cisplatin-based chemotherapy for treating bladder cancer. Full article

(This article belongs to the Special Issue Marine Natural Products as Regulators in Cell Signaling Pathway)

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22 pages, 1223 KiB

Open AccessArticle

Functional and Bioactive Benefits of Selected Microalgal Hydrolysates Assessed In Silico and In Vitro

by Elena Aurino, Leticia Mora, Antonio Marzocchella, Christina M. Kuchendorf, Bärbel Ackermann and Maria Hayes

Mar. Drugs 2025, 23(2), 53; https://doi.org/10.3390/md23020053 - 22 Jan 2025

Abstract

BIOPEP-UWM, a peptide database, contains 5128 peptides from a myriad of resources. Five listed peptides are Angiotensin-I-converting enzyme (ACE-1; EC3.4.15.1) inhibitory peptides derived from a red alga, while two from Chlorella vulgaris have anti-cancer and antioxidative bioactivities. Herein, we describe a process combining [...] Read more.

BIOPEP-UWM, a peptide database, contains 5128 peptides from a myriad of resources. Five listed peptides are Angiotensin-I-converting enzyme (ACE-1; EC3.4.15.1) inhibitory peptides derived from a red alga, while two from Chlorella vulgaris have anti-cancer and antioxidative bioactivities. Herein, we describe a process combining hydrolysis with two enzymes, Alcalase and Viscozyme, and filtration to generate protein-rich, bioactive peptide-containing hydrolysates from mixed species of Chlorella sp. and Scenedesmus sp. The potential of generated algal hydrolysates to act as food ingredients was determined by assessment of their techno-functional (foaming, emulsification, solubility, water holding, and oil holding capacity) properties. Bioactive screening of hydrolysates in vitro combined with mass spectrometry (MS) and in silico predictions identified bioactive and functional hydrolysates and six novel peptides. Peptides derived from Chlorella mix have the sequences YDYIGNNPAKGGLF and YIGNNPAKGGLF with predicted anti-inflammatory (medium confidence) and umami potential. Peptides from Scenedesmus mix have sequences IEWYGPDRPKFL, RSPTGEIIFGGETM, TVQIPGGERVPFLF, and IEWYGPDRPKFLGPF with predicted anti-inflammatory, anti-diabetic, and umami attributes. Such microalgal hydrolysates could provide essential amino acids to consumers as well as tertiary health benefits to improve human global health. Full article

(This article belongs to the Special Issue Marine Algal Biotechnology and Applications)

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21 pages, 1251 KiB

Open AccessReview

Production, Transport, Fate and Effects of Lipids in the Marine Environment

by Christopher C. Parrish

Mar. Drugs 2025, 23(2), 52; https://doi.org/10.3390/md23020052 - 21 Jan 2025

Abstract

Lipids form energy storage depots, cellular barriers and signaling molecules. They are generated and metabolized by enzymes under the influence of biotic and abiotic factors, and some—the long-chain polyunsaturated ω3 and ω6 fatty acids and cholesterol—are essential for optimal health in marine organisms. [...] Read more.

Lipids form energy storage depots, cellular barriers and signaling molecules. They are generated and metabolized by enzymes under the influence of biotic and abiotic factors, and some—the long-chain polyunsaturated ω3 and ω6 fatty acids and cholesterol—are essential for optimal health in marine organisms. In addition, lipids have direct and indirect roles in the control of buoyancy in marine fauna ranging from copepods to whales. Phytoplankton account for about half of the planet’s carbon fixation, and about half of that carbon goes into lipids. Lipids are an important component of the ocean’s ability to sequester carbon away from the atmosphere through sinking and especially after transfer to zooplankton. Phytoplankton are the main suppliers of ω3 polyunsaturated fatty acids (PUFAs) in the marine environment. They also supply cholesterol and many phytosterols to ocean ecosystems; however, genomics is indicating that members of the Cnidaria, Rotifera, Annelida, and Mollusca phyla also have the endogenous capacity for the de novo synthesis of ω3 PUFAs as well as phytosterols. It has been predicted that ω3 long-chain PUFAs will decrease in marine organisms with climate change, with implications for human consumption and for carbon sequestration; however, the responses of ω3 PUFA supply to future conditions are likely to be quite diverse. Full article

(This article belongs to the Special Issue Applications of Lipids from Marine Sources)

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21 pages, 1774 KiB

Open AccessArticle

Efficient Synthesis of Fused Polycyclic Ether Systems via Sulfonium Ylides: A Synthetic Approach to Yessotoxin and Adriatoxin

by Federico Moya-Utrera, Iván Cheng-Sánchez, Irama Fuentes-Pino, Antonio Sánchez-Ruiz and Francisco Sarabia

Mar. Drugs 2025, 23(2), 51; https://doi.org/10.3390/md23020051 - 21 Jan 2025

Abstract

A novel class of chiral sulfonium salts, derived from L- and D-methionine, was designed and successfully employed for the diastereoselective synthesis of epoxy amides. This new methodology of asymmetric epoxidation was exploited for the stereoselective construction of fused polycyclic ethers, which are structural [...] Read more.

A novel class of chiral sulfonium salts, derived from L- and D-methionine, was designed and successfully employed for the diastereoselective synthesis of epoxy amides. This new methodology of asymmetric epoxidation was exploited for the stereoselective construction of fused polycyclic ethers, which are structural motifs present in a great variety of natural products of marine origin. This methodology proved to be useful for the synthesis of the tricyclic A–C system contained in yessotoxin and adriatoxin, and also in many other related natural products of marine origin belonging to the fused polycyclic ether toxins. Full article

(This article belongs to the Special Issue Total Synthesis and Synthetic Approaches towards Marine Bioactive Natural Products and Analogues)

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15 pages, 2004 KiB

Open AccessArticle

Metabolic Blockade-Based Genome Mining of Malbranchea circinata SDU050: Discovery of Diverse Secondary Metabolites

by Hu Yang, Xiaowei Luo, Zhuo Shang, Kunlong Li, Jian Cai, Yingying Chen, Longchao Xin and Jianhua Ju

Mar. Drugs 2025, 23(1), 50; https://doi.org/10.3390/md23010050 - 20 Jan 2025

Abstract

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation [...] Read more.

Malbranchea circinata SDU050, a fungus derived from deep-sea sediment, is a prolific producer of diverse secondary metabolites. Genome sequencing revealed the presence of at least 69 biosynthetic gene clusters (BGCs), including 30 encoding type I polyketide synthases (PKSs). This study reports the isolation and identification of four classes of secondary metabolites from wild-type M. circinata SDU050, alongside five additional metabolite classes, including three novel cytochalasins (7–9), obtained from a mutant strain through the metabolic blockade strategy. Furthermore, bioinformatic analysis of the BGC associated with the isocoumarin sclerin (1) enabled the deduction of its biosynthetic pathway based on gene function predictions. Bioactivity assays demonstrated that sclerin (1) and (−)-mycousnine (10) exhibited weak antibacterial activity against Gram-positive bacteria such as Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Bacillus subtilis. These findings underscore the chemical diversity and biosynthetic potential of M. circinata SDU050 and highlight an effective strategy for exploring marine fungal metabolites. Full article

(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)

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23 pages, 9793 KiB

Open AccessArticle

Deep-Sea-Derived Isobisvertinol Targets TLR4 to Exhibit Neuroprotective Activity via Anti-Inflammatory and Ferroptosis-Inhibitory Effects

by Zi-Han Xu, Ming-Min Xie, Chun-Lan Xie, Xian-Wen Yang and Jun-Song Wang

Mar. Drugs 2025, 23(1), 49; https://doi.org/10.3390/md23010049 - 20 Jan 2025

Abstract

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, [...] Read more.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development. In this study, we isolated 44 natural products from deep-sea-derived fungi and identified isobisvertinol (17) as a compound with anti-inflammatory and ferroptosis-inhibiting effects. Using LPS-induced microglial inflammation and RSL3-induced neuronal ferroptosis models, we found that 17 targets TLR4 to provide neuroprotection. Molecular docking studies revealed that 17 inhibits TLR4 activation by occupying the hydrophobic pocket at the TLR4-MD2 binding site. Additionally, 17 suppresses TLR4, reducing p38 MAPK phosphorylation, and inhibits ferroptosis by decreasing lipid peroxidation and modulating mitochondrial membrane potential. Metabolomic analysis showed that 17 rescues alterations in multiple metabolic pathways induced by RSL3 and increases levels of antioxidant metabolites, including glutamine, glutamate, and glutathione. In summary, our results indicate that isobisvertinol (17) targets TLR4 in neural cells to reduce inflammation and inhibit p38 MAPK phosphorylation, while regulating metabolic pathways, mainly GSH synthesis, to provide antioxidant effects and prevent ferroptosis in neurons. Full article

(This article belongs to the Section Marine Pharmacology)

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16 pages, 2179 KiB

Open AccessArticle

Ishophloroglucin A Isolated from Ishige okamurae Protects Glomerular Cells from Methylglyoxal-Induced Diacarbonyl Stress and Inhibits the Pathogenesis of Diabetic Nephropathy

by Chi-Heung Cho, Min-Gyeong Kim, Bomi Ryu and Sang-Hoon Lee

Mar. Drugs 2025, 23(1), 48; https://doi.org/10.3390/md23010048 - 20 Jan 2025

Abstract

Ishige okamurae (I. okamuare), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of [...] Read more.

Ishige okamurae (I. okamuare), an edible brown alga, is rich in isophloroglucin A (IPA) phlorotannin compounds and is effective in preventing diseases, including diabetes. We evaluated its anti-glycation ability, intracellular reactive oxygen species scavenging activity, inhibitory effect on the accumulation of intracellular MGO/MGO-derived advanced glycation end products (AGE), and regulation of downstream signaling pathways related to the AGE–receptor for AGEs (RAGE) interaction. IPA (0.2, 1, and 5 μM) demonstrated anti-glycation ability by inhibiting the formation of glucose-fructose-BSA-derived AGEs by up to 54.63% compared to the untreated control, reducing the formation of irreversible cross-links between MGO-derived AGEs and collagen by 67.68% and the breaking down of existing cross-links by approximately 91% (p < 0.001). IPA protected cells from MGO-induced oxidative stress by inhibiting intracellular MGO accumulation (untreated cells: 1.62 μg/mL, MGO treated cells: 25.27 μg/mL, and IPA 5 μM: 11.23 μg/mL) (p < 0.001) and AGE generation and inhibited MGO-induced renal cell damage via the downregulation of MGO-induced RAGE protein expression (relative protein expression levels of MGO treated cells: 9.37 and IPA 5 μM:1.74) (p < 0.001). Overall, these results suggest that IPA has the potential to be utilized as a useful natural agent for the prevention and management of AGE-related diabetic nephropathy, owing to its strong anti-glycation activity. Full article

(This article belongs to the Special Issue Marine Natural Products in Anti-obesity and Metabolic Syndrome)

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14 pages, 5617 KiB

Open AccessArticle

Methyl 3-Bromo-4,5-dihydroxybenzoate Attenuates Inflammatory Bowel Disease by Regulating TLR/NF-κB Pathways

by Jing Huang, Lei Li, Liyan Xu, Lixin Feng, Yuxin Wang, Attila Gabor SIK, Meng Jin, Rongchun Wang, Kechun Liu and Xiaobin Li

Mar. Drugs 2025, 23(1), 47; https://doi.org/10.3390/md23010047 - 19 Jan 2025

Abstract

Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine [...] Read more.

Inflammatory bowel disease (IBD) is characterized by uncontrolled, chronic relapsing inflammation in the gastrointestinal tract and has become a global healthcare problem. Here, we aimed to illustrate the anti-inflammatory activity and the underlying mechanism of methyl 3-bromo-4,5-dihydroxybenzoate (MBD), a compound derived from marine organisms, especially in IBD, using a zebrafish model. The results indicated that MBD could inhibit the inflammatory responses induced by CuSO₄, tail amputation and LPS in zebrafish. Furthermore, MBD notably inhibited the intestinal migration of immune cells, enhanced the integrity of the gut mucosal barrier and improved intestinal peristalsis function in a zebrafish IBD model induced by trinitro-benzene-sulfonic acid (TNBS). In addition, MBD could inhibit ROS elevation induced by TNBS. Network pharmacology analysis, molecular docking, transcriptomics sequencing and RT-PCR were conducted to investigate the potential mechanism. The results showed that MBD could regulate the TLR/NF-κB pathways by inhibiting the mRNA expression of TNF-α, NF-κB, IL-1, IL-1β, IL6, AP1, IFNγ, IKKβ, MyD88, STAT3, TRAF1, TRAF6, NLRP3, NOD2, TLR3 and TLR4, and promoting the mRNA expression of IL4, IκBα and Bcl-2. In conclusion, these findings indicate that MBD could be a potential candidate for the treatment of IBD. Full article

(This article belongs to the Special Issue Marine-Derived Ingredients for Functional Foods)

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20 pages, 3444 KiB

Open AccessArticle

Antimicrobial Activities of Polysaccharide-Rich Extracts from the Irish Seaweed Alaria esculenta, Generated Using Green and Conventional Extraction Technologies, Against Foodborne Pathogens

by Ailbhe McGurrin, Rahel Suchintita Das, Arturo B. Soro, Julie Maguire, Noelia Flórez Fernández, Herminia Dominguez, Maria Dolores Torres, Brijesh K. Tiwari and Marco Garcia-Vaquero

Mar. Drugs 2025, 23(1), 46; https://doi.org/10.3390/md23010046 - 18 Jan 2025

Abstract

A rise in antimicrobial resistance coupled with consumer preferences towards natural preservatives has resulted in increased research towards investigating antimicrobial compounds from natural sources such as macroalgae (seaweeds), which contain antioxidant, antimicrobial, and anticancer compounds. This study investigates the antimicrobial activity of compounds [...] Read more.

A rise in antimicrobial resistance coupled with consumer preferences towards natural preservatives has resulted in increased research towards investigating antimicrobial compounds from natural sources such as macroalgae (seaweeds), which contain antioxidant, antimicrobial, and anticancer compounds. This study investigates the antimicrobial activity of compounds produced by the Irish seaweed Alaria esculenta against Escherichia coli and Listeria innocua, bacterial species which are relevant for food safety. Microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), ultrasound–microwave-assisted extraction (UMAE), and conventional extraction technologies (maceration) were applied to generate extracts from A. esculenta, followed by their preliminary chemical composition (total phenolic content, total protein content, total soluble sugars) and antimicrobial activity (with minimum inhibitory concentration determined by broth microdilution methods), examining also the molecular weight distribution (via high performance size exclusion chromatography) and oligosaccharide fraction composition (via high-performance liquid chromatography) of the polysaccharides, as they were the predominant compounds in these extracts, aiming to elucidate structure–function relationships. The chemical composition of the extracts demonstrated that they were high in total soluble sugars, with the highest total sugars being seen from the extract prepared with UAE, having 32.68 mg glucose equivalents/100 mg dried extract. Extracts had antimicrobial activity against E. coli and featured minimum inhibitory concentration (MIC) values of 6.25 mg/mL (in the case of the extract prepared with UAE) and 12.5 mg/mL (in the case of the extracts prepared with MAE, UMAE, and conventional maceration). No antimicrobial activity was seen by any extracts against L. innocua. An analysis of molar mass distribution of A. esculenta extracts showed high heterogeneity, with high-molecular-weight areas possibly indicating the presence of fucoidan. The FTIR spectra also indicated the presence of fucoidan as well as alginate, both of which are commonly found in brown seaweeds. These results indicate the potential of antimicrobials from seaweeds extracted using green technologies. Full article

(This article belongs to the Special Issue Marine Algae: Exploring Their Nutritional, Health, and Nutraceutical Potential)

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