Marine Drugs

17 pages, 3104 KiB

Open AccessArticle

Codium fragile Extract Ameliorates Respiratory Function by Controlling Allergic Inflammation in Ovalbumin-Induced Bronchial Disorders in Mice

by Hyo Lim Lee, Yeong Hyeon Ju, In Young Kim, Hye Ji Choi, Yu Mi Heo, Hwa Rang Na and Ho Jin Heo

Mar. Drugs 2025, 23(5), 221; https://doi.org/10.3390/md23050221 - 21 May 2025

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Abstract

This study investigated the effect of Codium fragile (WCF) water extract in reducing allergic inflammation in ovalbumin (OVA)-induced mice. Mice were sensitized to OVA + aluminum hydroxide, administered WCF for one week, and exposed to 1% aerosolized OVA. As a result, WCF intake [...] Read more.

This study investigated the effect of Codium fragile (WCF) water extract in reducing allergic inflammation in ovalbumin (OVA)-induced mice. Mice were sensitized to OVA + aluminum hydroxide, administered WCF for one week, and exposed to 1% aerosolized OVA. As a result, WCF intake reduced the OVA-induced increase in CD4⁺ T cells, CD8⁺ T cells, the T helper type 2 (Th2)/T helper type 1 (Th1) cell ratio, and inflammatory cells such as eosinophils and lymphocytes. Furthermore, WCF reduced Th2 cytokines such as interleukin (IL)-5, IL-13, and IL-33 and inflammatory cytokines such as tumor necrosis factor α (TNF-α) and IL-1β in lung tissues. A histological analysis showed that WCF intake decreases OVA-induced pulmonary inflammation, bronchial wall thickness, and mucus score and increases pulmonary alveolar area. Moreover, WCF inhibited the nuclear factor κB (NF-κB) pathway, the transforming growth factor β (TGF-β)/Smad pathway, and apoptosis-related proteins in lung tissues that OVA excessively activated. The oleamide (9-octadecenamide) content, representing a physiologically active component of WCF, was analyzed and validated using a high-performance liquid chromatography-photodiode array (HPLC-PDA) system. These results demonstrate that WCF may serve as a potential preventive agent for respiratory dysfunction such as allergic asthma by suppressing NF-κB and TGF-β/Smad pathways. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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11 pages, 991 KiB

Open AccessPerspective

The Enigma of Sponge-Derived Terpenoid Isothiocyanate–Thiocyanate Pairs: A Biosynthetic Proposal

by Tadeusz F. Molinski

Mar. Drugs 2025, 23(5), 220; https://doi.org/10.3390/md23050220 - 21 May 2025

Viewed by 540

Abstract

The co-occurrence of rare terpenoid thiocyanates (R-SCN), structurally similar to their more common isothiocyanate isomers (R-NCS), poses an enigma: how does the accepted path, terpenyl cation R⁺ → R-NC → R-NCS, accommodate R-SCN? The mystery can now be rationalized by the consideration [...] Read more.

The co-occurrence of rare terpenoid thiocyanates (R-SCN), structurally similar to their more common isothiocyanate isomers (R-NCS), poses an enigma: how does the accepted path, terpenyl cation R⁺ → R-NC → R-NCS, accommodate R-SCN? The mystery can now be rationalized by the consideration of three biosynthetic motifs: terpenoid carbocation (R⁺) capture by cyanoformate, NC-COOH (itself in equilibrium with NC⁻ and CO₂); co-localized rhodanese (a dual-function enzyme) that can both convert fugitive inorganic NC⁻ to thiocyanate ion, NCS⁻, and alkyl isonitriles to alkyl isothiocyanate (R-NC → R-NCS) and adventitious capture of the NCS⁻ by R⁺. The former two scenarios explain the preponderance of isothiocyanates, R-NCS, as products of a linear reaction path—the α-addition of S⁰ to R-NC—and the third scenario explains minor, less stable thiocyanates, R-SCN, as products of the adventitious capture of liberated NCS⁻ by the penultimate R⁺ precursor. DFT calculations support this proposal and eliminate other possibilities, e.g., the isomerization of R-NCS to R-SCN. Full article

(This article belongs to the Special Issue Biosynthesis of Biologically Active Marine Natural Products 2025)

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13 pages, 1859 KiB

Open AccessArticle

The Isolation, Structural Characterization, and Biosynthetic Pathway of Unguisin from the Marine-Derived Fungus Aspergillus candidus

by Wenjiao Diao, Wei Zhang, Xiaoxi Zhang, Siyu Du, Caijuan Zheng, Xuenian Huang and Xuefeng Lu

Mar. Drugs 2025, 23(5), 219; https://doi.org/10.3390/md23050219 - 21 May 2025

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Abstract

Unguisins, a class of structurally complex cyclic peptides featuring a γ-aminobutyric acid residue embedded in the skeleton, exhibit diverse biological activities. Here, a new unguisin K, along with three known congeners, was isolated from the marine-derived fungus Aspergillus candidus MEFC1001. The biosynthetic [...] Read more.

Unguisins, a class of structurally complex cyclic peptides featuring a γ-aminobutyric acid residue embedded in the skeleton, exhibit diverse biological activities. Here, a new unguisin K, along with three known congeners, was isolated from the marine-derived fungus Aspergillus candidus MEFC1001. The biosynthetic pathway was elucidated through gene disruption coupled with in vitro enzymatic characterization. The ugs biosynthetic gene cluster (BGC) containing ugsA and ugsB, in conjunction with an extra-clustered gene ugsC, collaborates to synthesize these unguisins. The alanine racemase (AR) UgsC catalyzes the isomerization of Ala and provides d-Ala as the starter unit for the non-ribosomal peptide synthetase (NRPS). The unique localization of ugsC outside the ugs BGC is different from previously reported unguisin-producing systems where AR genes reside within BGCs. The methyltransferase UgsB mediates a key pre-modification step by methylating phenylpyruvic acid to yield β-methylphenylpyruvate, which is subsequently incorporated as β-methylphenylalanine during NRPS assembly. This represents the first experimental evidence of the β-carbon methylation of Phe residue occurring at the precursor level rather than through post-assembly modification. The NRPS UgsA recruits a variety of amino acids for assembly and cyclization to form mature unguisins. Additionally, genome mining utilizing UgsA as a query identified homologous NRPSs in diverse fungal species, highlighting the potential for unguisin production in fungi. This study enriches the biosynthetic diversity of cyclic peptides and provides guidance for exploring unguisin-like natural products derived from fungi. Full article

(This article belongs to the Special Issue Biosynthesis of Biologically Active Marine Natural Products 2025)

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31 pages, 3605 KiB

Open AccessArticle

Bioactivity Assessment and Untargeted Metabolomics of the Mediterranean Sea Pen Pennatula phosphorea

by Silvia Scarpato, Daniel Venturi, Fortunato Palma Esposito, Maria Cristina Mangano, Gianluca Sarà, Francesco Margiotta, Ester Pagano, Maria Miraglia, Enrico Sangiovanni, Mercedes Garcia-Gil, Lorenzo Di Cesare Mannelli, Carla Ghelardini, Mario Dell’Agli, Angelo A. Izzo, Paola Nieri, Donatella de Pascale and Gerardo Della Sala

Mar. Drugs 2025, 23(5), 218; https://doi.org/10.3390/md23050218 - 21 May 2025

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Abstract

Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity [...] Read more.

Octocorals have proven to be a prolific source of bioactive natural products, exhibiting a wide spectrum of pharmacological activities. Among octocorals, Pennatulaceans, commonly known as sea pens, are among the most dominant soft coral species living in benthic communities. Nonetheless, reports on bioactivity and chemical investigations of this genus are scarce. This prompted us to shed light on the pharmacological potential of the extracts of the sea pen Pennatula phosphorea, Linneus 1758, and gain an overview of its metabolome. Crude octocoral extracts, obtained with a modified Kupchan extraction protocol, were assessed for their bioactivity potential, revealing the hexanic extract to exert anti-inflammatory effects and interesting protective properties in an in vitro model of sarcopenia and in auditory HEI-OC1 cisplatin-treated cells, while the chloroformic extract was active in reducing A375 melanoma cell viability in a concentration-dependent manner. An untargeted metabolomic analysis unveiled that P. phosphorea collects a wide array of glycerophospholipids and phosphosphingolipids belonging to the ceramide phosphoinositol class, which were exclusive or more abundant in the hexanic extract. Their proven anti-inflammatory and cytoprotective effects could demonstrate the activity shown by the P. phosphorea hexanic extract. In addition, a group of prostaglandins, eluted mainly in the chloroformic extract, were putatively annotated. Since prostanoids from marine origin have been demonstrated to exert cytotoxic and anti-proliferative properties against various cancer cell lines, the presence of PGs in the P. phosphorea chloroform extract could justify its anti-melanoma activity. This is the first report on the presence of glycerophospholipids, phosphosphingolipids, and prostaglandins, along with the identification of novel congeners, in sea pens. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

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17 pages, 4015 KiB

Open AccessArticle

Paralytic Shellfish Toxins in Coastal Waters of Changdao Island (China): Toxin Profiles, Potential Producers, and Environmental Conditions

by Guanchao Zheng, Yuxiang Deng, Haiyan Wu, Xiaokang Li, Ling Cheng, Chengxu Yuan, Minlu Liu and Zhijun Tan

Mar. Drugs 2025, 23(5), 217; https://doi.org/10.3390/md23050217 - 21 May 2025

Viewed by 531

Abstract

In recent decades, there have been frequent occurrences of paralytic shellfish toxin (PST) contamination in the Yellow and Bohai Seas, China. The waters around Changdao Island, situated at the convergence of these two seas, have suffered harmful algal blooms of Alexandrium spp., indicating [...] Read more.

In recent decades, there have been frequent occurrences of paralytic shellfish toxin (PST) contamination in the Yellow and Bohai Seas, China. The waters around Changdao Island, situated at the convergence of these two seas, have suffered harmful algal blooms of Alexandrium spp., indicating a potential risk of PST contamination in shellfish. However, a systematic investigation and assessment of PSTs in this area is still lacking. The presence of PSTs in plankton concentrates and shellfish in coastal areas of Changdao Island was monitored from April to October 2022, using liquid chromatography–tandem mass spectrometry. The potential toxin-producing microalgae were analyzed, as were the environmental conditions associated with their occurrence. The highest levels of PSTs in plankton concentrates and shellfish were both observed in September, reaching levels of 105.8 ng STXeq./L and 114.7 μg STXeq./kg, respectively. The main analogues were C1, C2, and GTX1–4. High-throughput analysis of the plankton concentrates identified eight species of Alexandrium, which are potential producers of PSTs. Sediment samples also revealed the presence of permanent cysts of Alexandrium. This research represents a significant advance in our understanding of the distribution and hypothetical sources of PSTs in the coastal waters of Changdao Island. Full article

(This article belongs to the Special Issue Emerging Toxins Accumulation in Shellfish)

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14 pages, 1806 KiB

Open AccessArticle

Chartarlactams U-X: Novel Phenylspirodrimanes from a Marine Derived Fungus Stachybotrys sp. SZU-W23 with Anti-Inflammatory Activity Mediated by the NF-κB/ROS Signaling Pathways

by Yanhua Wu, Lanyi Lu, Peng Zhang and Liyan Wang

Mar. Drugs 2025, 23(5), 216; https://doi.org/10.3390/md23050216 - 20 May 2025

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Abstract

In this investigation, the anti-inflammatory potential of phenylspirodrimanes (PSDs) produced by the marine-derived fungal strain Stachybotrys sp. SZU-W23 was systematically explored. A total of 15 PSDs were successfully isolated. Among them, four novel compounds, designated as chartarlactams U-X, were precisely characterized using NMR, [...] Read more.

In this investigation, the anti-inflammatory potential of phenylspirodrimanes (PSDs) produced by the marine-derived fungal strain Stachybotrys sp. SZU-W23 was systematically explored. A total of 15 PSDs were successfully isolated. Among them, four novel compounds, designated as chartarlactams U-X, were precisely characterized using NMR, HRESIMS, and ECD analyses. Specifically, compound 10 exhibited the most potent inhibitory effect on nitric oxide production in LPS-stimulated RAW 264.7 macrophages within the 0.3–30 μM concentration range, with an IC₅₀ value of 12.4 μM. Additionally, MTT assays revealed no detectable cytotoxicity at these concentrations. Mechanistic studies revealed that compound 10 effectively suppressed ROS generation, likely inactivating the NF-κB signaling pathway and consequently downregulating pro-inflammatory mediators, including iNOS, IL-6, and IL-1β. Full article

(This article belongs to the Special Issue Structural Diversity in Marine Natural Products)

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17 pages, 3430 KiB

Open AccessArticle

Reeler Domain-Containing Proteins Involved in the Antibacterial Immunity of Shrimp Litopenaeus vannamei

by Jianying Qi, Guoqing Dai, Huiling Xing, Zhibin Fu, Sheng Ke and Lili Shi

Mar. Drugs 2025, 23(5), 215; https://doi.org/10.3390/md23050215 - 20 May 2025

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Abstract

Like other invertebrates, Litopenaeus vannamei lacks adaptive immunity and relies mainly on innate immunity for defense against foreign pathogens. In this study, three distinct Reeler domain-containing molecules were discovered in L. vannamei, designated as LvReeler1, LvReeler2, and LvReeler3. Analysis [...] Read more.

Like other invertebrates, Litopenaeus vannamei lacks adaptive immunity and relies mainly on innate immunity for defense against foreign pathogens. In this study, three distinct Reeler domain-containing molecules were discovered in L. vannamei, designated as LvReeler1, LvReeler2, and LvReeler3. Analysis of tissue-specific expression patterns indicated that LvReeler1 showed predominant expression in the stomach, whereas LvReeler2 and LvReeler3 demonstrated peak transcriptional activity within gill tissues. The expression of these molecules was induced by Vibrio parahaemolyticus. In vivo interference with LvReelers expressions via dsRNA significantly increased the mortality rate of L. vannamei, while also leading to a marked increase in the bacterial load of V. parahaemolyticus in the gills. Additionally, recombinant proteins of LvReeler1 (rLvReeler1), LvReeler2 (rLvReeler2), and LvReeler3 (rLvReeler3) were successfully expressed in Escherichia coli. Antibacterial assays demonstrated that rLvReelers inhibited the growth of V. parahaemolyticus, Vibrio alginolyticus, and Vibrio harveyi, with rLvReeler3 exhibiting the strongest inhibitory activity. Scanning electron microscopy (SEM) observations revealed that rLvReeler3 caused bacterial aggregates to disintegrate after binding to V. parahaemolyticus and V. alginolyticus. In conclusion, LvReelers play an active role in the antimicrobial immune response of L. vannamei. 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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24 pages, 7095 KiB

Open AccessArticle

Targeting YY1-DR5 Axis by Pyripyropene O as a Novel Therapeutic Strategy Against Prostate Cancer: Molecular Mechanisms and In Vivo Zebrafish Validation

by Wenxuan Fang, Ying Chen, Mingyi Nie, Xuefeng Zhou, Yonghong Liu, Huaming Tao, Bin Yang and Xueni Wang

Mar. Drugs 2025, 23(5), 214; https://doi.org/10.3390/md23050214 - 19 May 2025

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Abstract

Background: Induction of apoptosis is an important strategy for the treatment of prostate cancer. DR5 is a member of the death receptor superfamily and targeting DR5 is an effective way to induce apoptosis. Pyripyropene O is a natural compound isolated from the marine [...] Read more.

Background: Induction of apoptosis is an important strategy for the treatment of prostate cancer. DR5 is a member of the death receptor superfamily and targeting DR5 is an effective way to induce apoptosis. Pyripyropene O is a natural compound isolated from the marine fungus Aspergillus fumigatus SCSIO 41220. We found it has anti-prostate cancer potential by inducing apoptosis; Methods: The effects of pyripyropene O on the viability, proliferation, cell cycle, apoptosis and migration of prostate cancer cells were investigated by MTT assay, plate clone formation assay, 3D cell sphere assay, flow cytometry and real-time cell analysis. Transmission electron microscopy was used to observe the changes in the internal structure of prostate cancer cells after treatment with pyripyropene O. After determining the mode of cell death, the mechanism of action of pyripyropene O on prostate cancer was further investigated using apoptotic protein microarray, western blot, qPCR, molecular docking, cellular immunofluorescence staining and cellular thermal shift assay. After explaining the mechanism of action of pyriproxyfen O, the in vivo absorption, distribution, metabolism, excretion and potential toxicity of pyriproxyfen O were investigated using ADMETLab 2.0 software. Finally, a zebrafish xenograft tumour model was developed to evaluate the anti-prostate cancer effects of pyriproxyfen O in vivo; Results: The experimental results at the cellular level showed that pyripyropene O inhibited the survival, proliferation and migration of prostate cancer cells, and also showed that pyripyropene O blocked the prostate cancer cell cycle at the G2/M phase and induced apoptosis. At the molecular level, pyripyropene O binds to the transcription factor YY1, promotes YY1 nuclear translocation, regulates the transcription level of DR5, a target gene of YY1, and upregulates the expression of DR5 mRNA and protein. The in vivo results showed that pyripyropene O effectively inhibited the development of prostate cancer in zebrafish; Conclusions: Pyripyropene O has a clear anti-prostate cancer effect at both cellular and animal levels, inhibiting the survival and proliferation of prostate cancer cells by binding to the transcription factor YY1 to activate the expression of DR5 to promote apoptosis, thus exerting an inhibitory effect on prostate cancer. Full article

(This article belongs to the Special Issue Marine Microorganisms Bioprospecting)

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22 pages, 6051 KiB

Open AccessArticle

Identification, Expression Profiling, Microbial Binding, and Agglutination Analyses of Two Cathepsin B Genes in Black Rockfish (Sebastes schlegelii)

by Xinghua Zhuang, Xingchun Li, Wenpeng Li, Xuan Xu, Fengjun Lin, Yiying Liu, Chonghui Chen, Xiaoxu Zhang, Pei Zhang, Chao Li and Qiang Fu

Mar. Drugs 2025, 23(5), 213; https://doi.org/10.3390/md23050213 - 18 May 2025

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Abstract

As a lysosomal cysteine protease of the papain subfamily, cathepsin B (CTSB) is characterized by its innate immune functions and hydrolytic activity. However, the functions of CTSB in the immune responses of teleosts remain to be clarified. In this study, two CTSB genes [...] Read more.

As a lysosomal cysteine protease of the papain subfamily, cathepsin B (CTSB) is characterized by its innate immune functions and hydrolytic activity. However, the functions of CTSB in the immune responses of teleosts remain to be clarified. In this study, two CTSB genes in S. schlegelii, SsCTSBa and SsCTSBb, were identified. Both SsCTSBa and SsCTSBb are composed of a 993 bp ORF encoding 330 amino acids. It was found in a phylogeny analysis that both genes form monophyletic clades with their orthologous counterparts of Honeycomb rockfish (Sebastes umbrosus). A synteny analysis indicated that the CTSB homologues were comparatively conserved during vertebrate evolution. Additionally, quantitative real-time PCR revealed the ubiquitous mRNA expression of SsCTSBa and SsCTSBb in all of the examined tissues, and substantially differential expression patterns could be observed following Aeromonas salmonicida infection. A subcellular localization analysis demonstrated that the distribution of SsCTSBa and SsCTSBb was mainly in the cytoplasm. Moreover, rSsCTSBa and rSsCTSBb showed strong binding to Poly(I:C) and exhibited diverse agglutination effects on different bacteria. Overall, these findings suggest that the CTSB genes in black rockfish might show essential functions in the host defense of teleosts against bacterial infections, providing valuable insights for further investigations into the immune mechanism of teleost CTSB. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

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15 pages, 3422 KiB

Open AccessArticle

Dihydrogeodin from Fennellia flavipes Modulates Platelet Aggregation via Downregulation of Calcium Signaling, αIIbβ₃ Integrins, MAPK, and PI3K/Akt Pathways

by Abdul Wahab Akram, Dae-Cheol Choi, Hyung-Kyu Chae, Sung Dae Kim, Dongmi Kwak, Bong-Sik Yun and Man Hee Rhee

Mar. Drugs 2025, 23(5), 212; https://doi.org/10.3390/md23050212 - 17 May 2025

Viewed by 636

Abstract

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, frequently arising from platelet hyperactivation and subsequent thrombus formation. Although conventional antiplatelet therapies are available, challenges, such as drug resistance and bleeding complications, require the development of novel agents. In this study, [...] Read more.

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide, frequently arising from platelet hyperactivation and subsequent thrombus formation. Although conventional antiplatelet therapies are available, challenges, such as drug resistance and bleeding complications, require the development of novel agents. In this study, dihydrogeodin (DHG) was isolated from Fennellia flavipes and evaluated using platelets derived from Sprague–Dawley rats. Platelet aggregation induced by collagen, adenosine diphosphate, or thrombin was assessed by light transmission aggregometry; DHG significantly reduced aggregation in a dose-dependent manner. Further assays demonstrated that DHG suppressed intracellular calcium mobilization, adenosine triphosphate release, and integrin αIIbβ₃-dependent fibrinogen binding, thereby impairing clot retraction. Western blot analysis revealed that DHG reduced the phosphorylation of mitogen-activated protein kinases (ERK, JNK, p38) and PI3K/Akt, indicating inhibition across multiple platelet-signaling pathways. Additionally, SwissADME-assisted pharmacokinetics predicted favorable properties without violations of the Lipinski (Pfizer) filter, Muegge (Bayer) filter, Ghose filter, Veber filter, and Egan filter, and network pharmacology revealed inhibition of calcium and MAPK pathways. These results highlight the potential of DHG as a novel antiplatelet agent with broad-spectrum activity and promising drug-like characteristics. Further studies are warranted to assess its therapeutic window, safety profile, and potential for synergistic use with existing antiplatelet drugs. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 2nd Edition)

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17 pages, 1271 KiB

Open AccessReview

Deep Eutectic Systems: A Game Changer for Marine Bioactives Recovery

by Sandro Amador, Alice Martins, Margarida Matias, Rui Pedrosa and Susete Pinteus

Mar. Drugs 2025, 23(5), 211; https://doi.org/10.3390/md23050211 - 16 May 2025

Viewed by 935

Abstract

The extraction of bioactive compounds from marine natural products has gained increasing attention due to their diverse applications, such as in pharmaceuticals, nutraceuticals, and cosmetics. Yet, low extraction yields and toxicity associated with common solvents are a major bottleneck. Deep eutectic solvents (DESs) [...] Read more.

The extraction of bioactive compounds from marine natural products has gained increasing attention due to their diverse applications, such as in pharmaceuticals, nutraceuticals, and cosmetics. Yet, low extraction yields and toxicity associated with common solvents are a major bottleneck. Deep eutectic solvents (DESs) and natural deep eutectic solvents (NADESs) have emerged as promising green alternatives to conventional organic solvents, offering advantages such as biodegradability, greater environmental and economic sustainability, low toxicity, and enhanced extraction selectivity. This review provides a comprehensive analysis of the principles, physicochemical properties, and applications of DESs/NADESs to obtain bioactive compounds from marine organisms. Among the most recent works, it is possible to verify the success of NADESs to extract carrageenan from the seaweed Kappaphycus alvarezii; pigments from Palmaria palmata; and polyphenols and proteins from different brown seaweeds. NADESs have also shown high potential to extract other valuable compounds from marine by-products, such as chitin from crabs and shrimp shells, and also lipids and proteins from different fish species and protein rich extracts from tilapia viscera. The challenges for DESs/NADESs use at industrial scale are also discussed, and success cases are revealed, highlighting their potential as game changers for extracting bioactive compounds from marine organisms and driving the development of innovative biotechnological products. Full article

(This article belongs to the Special Issue Eutectic Solvents as Alternatives for Extracting Biologically Active Compounds from Marine Natural Products)

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22 pages, 5066 KiB

Open AccessReview

Sesquiterpenes from Brown Algae

by Irene Moreno-Gutiérrez, Sonia Berenguel-Gómez, Manuel Muñoz-Dorado, Míriam Álvarez-Corral and Ignacio Rodríguez-García

Mar. Drugs 2025, 23(5), 210; https://doi.org/10.3390/md23050210 - 15 May 2025

Viewed by 639

Abstract

Algae are the group that has managed to generate the largest number of compounds and secondary metabolites with different properties, many of them only present in the aquatic kingdom. Among them, brown algae are one of the main producers within marine ecosystems. Furthermore, [...] Read more.

Algae are the group that has managed to generate the largest number of compounds and secondary metabolites with different properties, many of them only present in the aquatic kingdom. Among them, brown algae are one of the main producers within marine ecosystems. Furthermore, one of the main groups of secondary metabolites studied are sesquiterpenes due to the great variety of properties observed, largely due to the great structural variability of these compounds. Many studies have been carried out to isolate and characterize compounds with a sesquiterpene structure from different species of brown algae. This article reviews the natural occurrence of sesquiterpene and derivatives in brown algae. A total of 51 sesquiterpenes isolated from brown algae, having monocyclic, bicyclic, or tricyclic skeletons, as well as 23 sesquiterpenoids with various chemical structures, are depicted. Moreover, there are at least eleven publications focused on the study of the profiles on volatile organic compounds (VOCs) within brown algae, derived using several analytic and extraction techniques, and in the finding of a large variety of structures of sesquiterpenes. Full article

(This article belongs to the Special Issue Nutritional Content, Biologically Active Compounds, and Correlated Health Impacts of Seaweed as a Resource for Nutraceutical, Cosmetic, and Pharmaceutical Applications)

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33 pages, 25820 KiB

Open AccessArticle

Novel Anti-MRSA Peptide from Mangrove-Derived Virgibacillus chiguensis FN33 Supported by Genomics and Molecular Dynamics

by Namfa Sermkaew, Apichart Atipairin, Phetcharat Boonruamkaew, Sucheewin Krobthong, Chanat Aonbangkhen, Jumpei Uchiyama, Yodying Yingchutrakul and Nuttapon Songnaka

Mar. Drugs 2025, 23(5), 209; https://doi.org/10.3390/md23050209 - 14 May 2025

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Abstract

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a [...] Read more.

Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH₃-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30–40 °C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a β-sheet structure upon membrane interaction. These findings suggest that Virgibacillus chiguensis FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections. Full article

(This article belongs to the Special Issue Research on Marine Antimicrobial Peptides)

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25 pages, 3401 KiB

Open AccessArticle

Biochemical Composition and Alkaline Extraction Optimization of Soluble Bioactive Compounds from the Green Algae Caulerpa cylindraceae

by Amani Tahar, Haïfa Zghida, Débora Tomazi Pereira, Nathalie Korbee, Helen Treichel, Félix L. Figueroa and Lotfi Achour

Mar. Drugs 2025, 23(5), 208; https://doi.org/10.3390/md23050208 - 14 May 2025

Viewed by 554

Abstract

There is a growing interest in studying the bioactive compounds of invasive green macroalga Caulerpa cylindracea due to their potential biotechnological applications. Algal samples were collected from two sites and seasons. Elemental analysis showed the abundance of carbon in the raw material as [...] Read more.

There is a growing interest in studying the bioactive compounds of invasive green macroalga Caulerpa cylindracea due to their potential biotechnological applications. Algal samples were collected from two sites and seasons. Elemental analysis showed the abundance of carbon in the raw material as a source of carbohydrates. The total protein content in different samples ranged from 8.17 to 9.98%. Total lipids in different samples were around 2%. Fatty acid (FA) results revealed the presence of various types, including omega-3 and omega-6 PUFA. Furthermore, an alkaline hydrolysis optimization using response surface methodology was investigated to extract soluble compounds. It showed that the best combination for polyphenols and ABTS was 12.5% sodium carbonate (SC) at 100 °C for 8 h; however, the best combination for proteins and carbohydrates was 7.5% SC at 100 °C for 5 h. A combination of ultrasound pretreatments was carried out to assess the enhancement of the contents. Thus, an increasing amount was recorded for polyphenols and antioxidant capacity. Ultrasound pretreatment results in decreasing extraction time for all compounds. Results showed that the invasive seaweeds, causing environmental impacts in the Mediterranean Sea, represent an interesting source of bioactive compounds. Full article

(This article belongs to the Special Issue New Methods in Extraction and Isolation of Marine Natural Products)

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35 pages, 1749 KiB

Open AccessReview

Marine-Derived Compounds Combined with Nanoparticles: A Focus on the Biomedical and Pharmaceutical Sector

by Laura M. Teixeira, Catarina P. Reis and Rita Pacheco

Mar. Drugs 2025, 23(5), 207; https://doi.org/10.3390/md23050207 - 13 May 2025

Viewed by 836

Abstract

The ocean is an extraordinary natural source of a wide range of bioactive compounds. These compounds, including proteins, phenolics, polysaccharides, pigments, vitamins, and fatty acids, possess unique biological properties that are increasingly being explored in the field of nanotechnology across diverse sectors. Among [...] Read more.

The ocean is an extraordinary natural source of a wide range of bioactive compounds. These compounds, including proteins, phenolics, polysaccharides, pigments, vitamins, and fatty acids, possess unique biological properties that are increasingly being explored in the field of nanotechnology across diverse sectors. Among marine-derived nanoparticles, promising applications have emerged in the biomedical and pharmaceutical fields, particularly metallic nanoparticles and polysaccharide-based drug delivery systems. This review provides a unique perspective on the integration of two research areas: the exploration of marine bioresources as bioactive compounds sources with nanotechnological methodologies to develop sustainable, safe, stable and functional marine-derived NPs. It highlights recent advancements in the green synthesis of MNPs and the formulation of drug delivery systems using marine polysaccharides. This review also describes the recent trends over the past ten years and discusses the major challenges and limitations associated with these approaches, including variability in biological sources, batch-to-batch inconsistency, mechanistic uncertainties, and difficulties in reproducibility and scalability. Furthermore, it emphasizes the need for standardized protocols and the integration of life cycle assessments (LCA) to evaluate environmental and economic viability for effective translating marine-derives nanoparticles from research to clinical applications. Full article

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

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23 pages, 2645 KiB

Open AccessReview

Antioxidant and Anti-Inflammatory Properties of Four Native Mediterranean Seagrasses: A Review of Bioactive Potential and Ecological Context

by Marzia Vasarri, Lucia De Marchi, Carlo Pretti, Emanuela Barletta and Donatella Degl’Innocenti

Mar. Drugs 2025, 23(5), 206; https://doi.org/10.3390/md23050206 - 12 May 2025

Cited by 1 | Viewed by 568

Abstract

This review provides current knowledge of the potential benefits of native Mediterranean seagrasses for human health, specifically focusing on their anti-inflammatory and antioxidant properties. The four main species examined—Posidonia oceanica, Cymodocea nodosa, Zostera marina, and Zostera noltii—are integral [...] Read more.

This review provides current knowledge of the potential benefits of native Mediterranean seagrasses for human health, specifically focusing on their anti-inflammatory and antioxidant properties. The four main species examined—Posidonia oceanica, Cymodocea nodosa, Zostera marina, and Zostera noltii—are integral components of marine ecosystems, providing essential habitats and supporting biodiversity. Recent studies highlight their rich bioactive compounds that show significant therapeutic potential against oxidative stress and chronic inflammation, which are prevalent in various health disorders. This overview synthesizes the current literature, emphasizing the mechanisms through which these seagrasses exert their beneficial effects. Furthermore, it addresses the environmental implications of the excessive use and abuse of conventional anti-inflammatory drugs, advocating for a shift towards natural alternatives derived from marine resources. By exploring the bioactivity of these Mediterranean seagrasses, research here collected underscores the importance of integrating marine plants into health and wellness strategies, thereby promoting both human health and ecosystem sustainability. This exploration not only enriches the understanding of their applications on human health but also stimulates further research in this promising field, paving the way for innovative approaches to combat chronic diseases and support environmental conservation. Full article

(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)

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11 pages, 1625 KiB

Open AccessArticle

A VioA Variant Activates Antibiotic Streptogramins in the Heterologous Host Streptomyces sp. OUC20-O

by Jie Shan, Liangguang Yue, Luyao Xu, Runyi Wang, Qingzhou Meng, Jun Feng, Joon-Hee Lee, Ming Lu and Huayue Li

Mar. Drugs 2025, 23(5), 205; https://doi.org/10.3390/md23050205 - 11 May 2025

Viewed by 507

Abstract

Heterologous expression of the G231L variant of VioA into 16 strains of marine-derived Streptomyces, combined with bioactivity tracking, leads to the activation of seven antibiotic streptogramins (1–7) in Streptomyces sp. OUC20-O. Among these, compound 1, named linstreptogramin, [...] Read more.

Heterologous expression of the G231L variant of VioA into 16 strains of marine-derived Streptomyces, combined with bioactivity tracking, leads to the activation of seven antibiotic streptogramins (1–7) in Streptomyces sp. OUC20-O. Among these, compound 1, named linstreptogramin, is a new compound with an unusual linear streptogramin skeleton. The planar structure and stereochemistry of compound 1 were established based on extensive MS and NMR spectroscopic analyses, together with ECD calculations. In the antibacterial activity evaluation, compounds 1–4 showed significant growth inhibition against the multidrug-resistant Enterococcus faecium CCARM 5203 with MIC values of 0.2–1.6 µg/mL, which are comparable to the positive control vancomycin. Full article

(This article belongs to the Special Issue Marine Microorganisms Bioprospecting)

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13 pages, 1074 KiB

Open AccessArticle

Stage-Specific Effects of TiO₂, ZnO, and CuO Nanoparticles on Green Microalga Haematococcus lacustris: Biomass and Astaxanthin Biosynthesis

by Ludmila Rudi, Tatiana Chiriac, Liliana Cepoi, Svetlana Djur and Ana Valuta

Mar. Drugs 2025, 23(5), 204; https://doi.org/10.3390/md23050204 - 11 May 2025

Viewed by 539

Abstract

Evaluating the effects of nanoparticles on biomass growth and astaxanthin accumulation in Haematococcus lacustris is crucial for optimizing the production of astaxanthin, a valuable carotenoid with numerous industrial applications. Identifying the life stages at which these nanoparticles exert stimulatory or toxic effects will [...] Read more.

Evaluating the effects of nanoparticles on biomass growth and astaxanthin accumulation in Haematococcus lacustris is crucial for optimizing the production of astaxanthin, a valuable carotenoid with numerous industrial applications. Identifying the life stages at which these nanoparticles exert stimulatory or toxic effects will aid in formulating effective production strategies. This study investigated the effects of titanium dioxide (TiO₂), zinc oxide (ZnO), and copper oxide (CuO) nanoparticles on biomass growth, astaxanthin biosynthesis, and lipid accumulation in Haematococcus lacustris, with a focus on their stage-specific impact throughout the algal life cycle. The nanoparticles were added at the start of cultivation, and the microalgal cultures developed continuously in their presence. Sampling for biochemical analyses was performed at distinct life stages (green motile, palmella, and aplanospore), enabling the assessment of stage-dependent responses. TiO₂NPs significantly stimulated biomass accumulation during the green motile stage. In the palmella stage, astaxanthin levels decreased in the presence of all nanoparticles, likely due to the absence of a stress signal required to activate pigment biosynthesis, despite ongoing biomass growth. In contrast, the aplanospore stage exhibited reactivation of astaxanthin biosynthesis and increased lipid accumulation, particularly under TiO₂NPs. Astaxanthin content increased by 21.57%. This study highlights that TiO₂, ZnO, and CuO nanoparticles modulate growth and astaxanthin biosynthesis in Haematococcus lacustris in a life cycle-dependent manner. Full article

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

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22 pages, 2824 KiB

Open AccessArticle

Metabolic Responses of Pyropia haitanensis to Dehydration-Rehydration Cycles Revealed by Metabolomics

by Jian Wen, Jianzhi Shi, Muhan Meng, Kai Xu, Yan Xu, Dehua Ji, Wenlei Wang and Chaotian Xie

Mar. Drugs 2025, 23(5), 203; https://doi.org/10.3390/md23050203 - 8 May 2025

Cited by 1 | Viewed by 656

Abstract

Pyropia haitanensis (T.J. Chang and B.F. Zheng) undergoes periodic dehydration and rehydration cycles, necessitating robust adaptive mechanisms. Despite extensive research on its physiological responses to desiccation stress, the comprehensive metabolic pathways and recovery mechanisms post-rehydration remain poorly understood. This study investigated the metabolic [...] Read more.

Pyropia haitanensis (T.J. Chang and B.F. Zheng) undergoes periodic dehydration and rehydration cycles, necessitating robust adaptive mechanisms. Despite extensive research on its physiological responses to desiccation stress, the comprehensive metabolic pathways and recovery mechanisms post-rehydration remain poorly understood. This study investigated the metabolic responses of P. haitanensis to varying degrees of desiccation stress using LC-MS and UPLC-MS/MS. Under mild dehydration, the thallus primarily accumulated sugars and proline, while moderate and severe dehydration triggered the accumulation of additional osmoprotectants like alanine betaine and trehalose to maintain turgor pressure and water retention. Concurrently, the alga activated a potent antioxidant system, including enzymes and non-enzymatic antioxidants, to counteract the increased reactive oxygen species levels and prevent oxidative damage. Hormonal regulation also plays a crucial role in stress adaptation, with salicylic acid and jasmonic acid upregulating under mild dehydration and cytokinins and gibberellin GA₁₅ accumulating under severe stress. Rehydration triggered the recovery process, with indole acetic acid, abscisic acid, and jasmonic acid promoting rapid cell recovery. Additionally, arachidonic acid, acting as a signaling molecule, induced general stress resistance, facilitating the adaptation of the thallus to the dynamic intertidal environment. These findings reveal P. haitanensis’ metabolic adaptation strategies in intertidal environments, with implications for enhancing cultivation and stress resistance in this economically important seaweed. Full article

(This article belongs to the Special Issue Molecular Metabolisms and Regulations of Marine Algae)

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18 pages, 10890 KiB

Open AccessArticle

Whole-Genome Sequence Analysis, Probiotic Potential, and Safety Assessment of the Marine Bacterium Paraliobacillus zengyii CGMCC1.16464

by Qianjin Fan, Mengqi Jiao, Haoyue Huangfu, Lan Chen, Beijie Li, Zhijie Cao, Xuelian Luo and Jianguo Xu

Mar. Drugs 2025, 23(5), 202; https://doi.org/10.3390/md23050202 - 7 May 2025

Viewed by 627

Abstract

Paraliobacillus zengyii CGMCC1.16464 (P. zengyii) is a novel antiviral probiotic candidate strain. To ensure its safety as a potential probiotic, a safety evaluation was conducted in this study. The safety and functional potential of P. zengyii were systematically assessed through genomic [...] Read more.

Paraliobacillus zengyii CGMCC1.16464 (P. zengyii) is a novel antiviral probiotic candidate strain. To ensure its safety as a potential probiotic, a safety evaluation was conducted in this study. The safety and functional potential of P. zengyii were systematically assessed through genomic bioinformatics analysis, in vitro experiments, and acute oral toxicity tests in mice. Genomic analysis revealed that P. zengyii is rich in genes related to carbohydrate and amino acid metabolisms and carries genes encoding antimicrobial and antiviral agents (such as ectoine, type III polyketide synthase, and lasso peptides). It also expresses gastrointestinal tolerance-related proteins (ClpC, GroEL, and ClpP). Its resistance to polymyxins is an inherent trait with no risk of plasmid-mediated transfer. In vitro experiments confirmed that P. zengyii is somewhat tolerant to bile salts and acidic environments and does not exhibit hemolytic or gelatinase activity. Importantly, an acute oral toxicity test in mice revealed that after intervention with high, medium, or low doses, no significant abnormalities in the body weight, organ index, or tissue morphology of the mice were observed. In conclusion, P. zengyii exhibited good safety and probiotic potential in terms of genomic safety, metabolic function, and in vitro and in vivo toxicities, providing a theoretical basis for the development of novel functional probiotics. Full article

(This article belongs to the Section Marine Biotechnology Related to Drug Discovery or Production)

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46 pages, 4970 KiB

Open AccessReview

Phycobilins Versatile Pigments with Wide-Ranging Applications: Exploring Their Uses, Biological Activities, Extraction Methods and Future Perspectives

by Celestino García-Gómez, Diana E. Aguirre-Cavazos, Abelardo Chávez-Montes, Juan M. Ballesteros-Torres, Alonso A. Orozco-Flores, Raúl Reyna-Martínez, Ángel D. Torres-Hernández, Georgia M. González-Meza, Sandra L. Castillo-Hernández, Marcela A. Gloria-Garza, Miroslava Kačániová, Maciej Ireneusz-Kluz and Joel H. Elizondo-Luevano

Mar. Drugs 2025, 23(5), 201; https://doi.org/10.3390/md23050201 - 4 May 2025

Viewed by 1424

Abstract

Phycobiliproteins (PBPs), captivating water-soluble proteins found in cyanobacteria, red algae, and cryptophytes, continue to fascinate researchers and industries due to their unique properties and multifaceted applications. These proteins consist of chromophores called phycobilins (PBs), covalently linked to specific protein subunits. Major phycobiliproteins include [...] Read more.

Phycobiliproteins (PBPs), captivating water-soluble proteins found in cyanobacteria, red algae, and cryptophytes, continue to fascinate researchers and industries due to their unique properties and multifaceted applications. These proteins consist of chromophores called phycobilins (PBs), covalently linked to specific protein subunits. Major phycobiliproteins include phycocyanin (PC), allophycocyanin (APC), and phycoerythrin (PE), each distinguished by distinct absorption and emission spectra. Beyond their colorful properties, PBs exhibit a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, and antidiabetic effects, making them valuable for pharmaceutical, biotechnological, and medical purposes. The extraction and purification methods for PBs have been optimized to enhance their bioavailability and stability, opening new avenues for industrial production. For this review, a comprehensive literature search was conducted using scientific databases such as PubMed, Scopus, and Web of Science, prioritizing peer-reviewed articles published between 2000 and 2025, with an emphasis on recent advances from the last five years, using keywords such as “phycobiliproteins”, “phycobilins”, “bioactivities”, “therapeutic applications”, and “industrial use”. Studies were selected based on their relevance to the biological, technological, and pharmacological applications of PBPs and PBs. This review explores the diverse applications of PBs in therapeutic, diagnostic, and environmental fields, highlighting their potential as natural alternatives in the treatment of various diseases. The future perspectives for PBs focus on their incorporation into innovative drug delivery systems, biocompatible materials, and functional foods, presenting exciting opportunities for advancing human health and well-being. Full article

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

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28 pages, 8350 KiB

Open AccessReview

Jellyfish Collagen in the Mediterranean Spotlight: Transforming Challenges into Opportunities

by Ainara Ballesteros, Raquel Torres, Maria Pascual-Torner, Francisco Revert-Ros, Jose Tena-Medialdea, José Rafael García-March, Josep Lloret and Josep-Maria Gili

Mar. Drugs 2025, 23(5), 200; https://doi.org/10.3390/md23050200 - 3 May 2025

Viewed by 1864

Abstract

Research increasingly highlights jellyfish as a sustainable alternative to other animal species, particularly for its collagen, which has versatile applications in blue biotechnology. This review explores the properties of jellyfish-derived collagen, extraction techniques, and its diverse industrial applications based on the current scientific [...] Read more.

Research increasingly highlights jellyfish as a sustainable alternative to other animal species, particularly for its collagen, which has versatile applications in blue biotechnology. This review explores the properties of jellyfish-derived collagen, extraction techniques, and its diverse industrial applications based on the current scientific literature. With a particular focus on research in the Mediterranean Sea, we underscore the role of the order Rhizostomeae as jellyfish species with high collagen content and provide an overview of the main sources for jellyfish harvesting, including active fishing, by-catch, and aquaculture. In the Mediterranean basin, the blooming species Rhizostoma pulmo, Cotylorhiza tuberculata, and Rhopilema nomadica represent a valuable opportunity to harness their nutraceutical benefits, as well as their potential for the development of biomaterials in tissue engineering and regenerative medicine. Although jellyfish fishing is not yet well-established in the region, ongoing collaborative projects with fishermen’s guilds are focused on promoting circular and blue economy strategies to valorize jellyfish as an innovative resource. Additionally, jellyfish aquaculture emerges as a promising alternative for ensuring a sustainable supply, with the Rhizostomeae Cassiopea spp. demonstrating significant potential for biotechnological applications. Full article

(This article belongs to the Special Issue Marine Collagen: From Biological Insights to Biomedical Breakthroughs)

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20 pages, 1126 KiB

Open AccessSystematic Review

Dental Resin Composites Modified with Chitosan: A Systematic Review

by Wojciech Dobrzyński, Paweł J. Piszko, Jan Kiryk, Sylwia Kiryk, Mateusz Michalak, Agnieszka Kotela, Julia Kensy, Witold Świenc, Natalia Grychowska, Jacek Matys and Maciej Dobrzyński

Mar. Drugs 2025, 23(5), 199; https://doi.org/10.3390/md23050199 - 1 May 2025

Viewed by 1000

Abstract

Objective: This systematic review aims to evaluate the impact of incorporating chitosan into dental resin composites on their mechanical, antibacterial, and physicochemical properties. Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted in March 2025 using the following [...] Read more.

Objective: This systematic review aims to evaluate the impact of incorporating chitosan into dental resin composites on their mechanical, antibacterial, and physicochemical properties. Methods: A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted in March 2025 using the following keywords: resin, composite, and chitosan. The inclusion criteria comprised in vitro studies in dentistry evaluating chitosan as a composite additive with full-text availability in English. Data extraction and quality assessment were performed independently by multiple reviewers using standardized tools, and study quality was assessed based on predefined criteria. Results: Seventeen studies met the inclusion criteria. Chitosan concentrations in the composites ranged from 0.25 wt% to 20 wt%. Antibacterial activity was confirmed in six studies, especially against S. mutans, S. sanguinis, and L. acidophilus. Mechanical properties such as fracture toughness, hardness, and compressive strength were generally improved at lower concentrations of chitosan. However, increased chitosan levels were associated with decreased flexural strength and increased microleakage. Shear bond strength (SBS) was unaffected by chitosan in low concentrations (up to 0.25%), while higher concentrations reduced SBS. Fluoride release capacity was assessed in one study, with no significant differences observed. Conclusion: Chitosan-modified dental resin composites exhibit promising antibacterial and mechanical enhancements at low concentrations. However, higher chitosan levels may compromise certain mechanical and adhesive properties. These findings suggest a need for standardized methodologies and further research on long-term clinical implications and fluoride release. Full article

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

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17 pages, 5225 KiB

Open AccessArticle

Improvement of Catalytic Activity and Thermostability of Alginate Lyase VxAly7B-CM via Rational Computational Design Strategies

by Xin Ma, Ke Zhu, Kaiyang Wang, Wenhui Liao, Xiaohan Yang, Wengong Yu, Weishan Wang and Feng Han

Mar. Drugs 2025, 23(5), 198; https://doi.org/10.3390/md23050198 - 1 May 2025

Viewed by 771

Abstract

Alginate lyase degrades alginate through the β-elimination mechanism to produce alginate oligosaccharides (AOS) with notable biochemical properties and diverse biological activities. However, its poor thermostability limits large-scale industrial production. In this study, we employed a rational computational design strategy combining computer-aided evolutionary coupling [...] Read more.

Alginate lyase degrades alginate through the β-elimination mechanism to produce alginate oligosaccharides (AOS) with notable biochemical properties and diverse biological activities. However, its poor thermostability limits large-scale industrial production. In this study, we employed a rational computational design strategy combining computer-aided evolutionary coupling analysis and ΔΔG_fold evaluation to enhance both the thermostability and catalytic activity of the alginate lyase VxAly7B-CM. Among ten single-point mutants, the E188N and S204G mutants exhibited increases in T_m from 47.0 °C to 48.9 °C and 50.2 °C, respectively, with specific activities of 3701.02 U/mg and 2812.01 U/mg at 45 °C. Notably, the combinatorial mutant E188N/S204G demonstrated a ΔT_m of 5 °C and an optimal reaction temperature up to 50 °C, where its specific activity reached 3823.80 U/mg—a 31% increase. Moreover, its half-life at 50 °C was 38.4 h, which is 7.0 times that of the wild-type enzyme. Protein structural analysis and molecular dynamics simulations suggested that the enhanced catalytic performance and thermostability of the E188N/S204G mutant may be attributed to optimized surface charge distribution, strengthened hydrophobic interactions, and increased tertiary structure stability. Overall, our findings provided valuable insights into enzyme stabilization strategies and supported the industrial production of functional AOS. Full article

(This article belongs to the Special Issue Research on Seaweed-Degrading Enzymes)

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36 pages, 8197 KiB

Open AccessReview

The Cytotoxic Activity of Secondary Metabolites from Marine-Derived Penicillium spp.: A Review (2018–2024)

by Shuncun Zhang, Huannan Wang, Chunmei Sai, Yan Wang, Zhongbin Cheng and Zhen Zhang

Mar. Drugs 2025, 23(5), 197; https://doi.org/10.3390/md23050197 - 30 Apr 2025

Viewed by 1099

Abstract

Marine-derived Penicillium spp., including Penicillium citrinum, Penicillium chrysogenum, and Penicillium sclerotiorum, have emerged as prolific producers of structurally diverse secondary metabolites with cytotoxic activity. This review systematically categorizes 177 bioactive compounds isolated from marine Penicillium spp. between 2018 and 2024, [...] Read more.

Marine-derived Penicillium spp., including Penicillium citrinum, Penicillium chrysogenum, and Penicillium sclerotiorum, have emerged as prolific producers of structurally diverse secondary metabolites with cytotoxic activity. This review systematically categorizes 177 bioactive compounds isolated from marine Penicillium spp. between 2018 and 2024, derived from diverse marine environments such as sediments, animals, plants, and mangroves. These compounds, classified into polyketides, alkaloids, terpenoids, and steroids, exhibit a wide range of cytotoxic activities. Their potency is categorized as potent (<1 μM or <0.5 μg/mL), notable (1–10 μM or 0.5–5 μg/mL), moderate (10–30 μM or 5–15 μg/mL), mild (30–50 μM or 15–25 μg/mL), and negligible (>50 μM or >25 μg/mL). The current review highlights the promising role of marine Penicillium spp. as a rich repository for the discovery of anticancer agents and the advancement of marine-inspired drug development. Full article

(This article belongs to the Special Issue Celebrating the 100th Anniversary of Ocean University of China: Potential Therapeutic Benefits of Marine Novel Natural Products)

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21 pages, 4309 KiB

Open AccessArticle

Identification of TRPV1-Inhibitory Peptides from Takifugu fasciatus Skin Hydrolysate and Their Skin-Soothing Mechanisms

by Haiyan Tang, Bei Chen, Dong Zhang, Ruowen Wu, Kun Qiao, Kang Chen, Yongchang Su, Shuilin Cai, Min Xu, Shuji Liu and Zhiyu Liu

Mar. Drugs 2025, 23(5), 196; https://doi.org/10.3390/md23050196 - 29 Apr 2025

Viewed by 797

Abstract

Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from Takifugu fasciatus skin for transient receptor potential vanilloid 1 (TRPV1)-inhibitory and anti-inflammatory activities and investigated their mechanisms in alleviating sensitive skin (SS). A low-molecular-weight hydrolysate was prepared through [...] Read more.

Skin sensitivity is increasingly prevalent, necessitating new therapeutic agents. This study screened multifunctional peptides from Takifugu fasciatus skin for transient receptor potential vanilloid 1 (TRPV1)-inhibitory and anti-inflammatory activities and investigated their mechanisms in alleviating sensitive skin (SS). A low-molecular-weight hydrolysate was prepared through enzymatic hydrolysis of T. fasciatus skin, followed by ultrafiltration, with subsequent peptide identification performed using nano-HPLC-MS/MS and molecular docking-based virtual screening. Among 20 TRPV1-antagonistic peptides (TFTIPs), QFF (T10), LDIF (T14), and FFR (T18) exhibited potent anti-inflammatory effects in (lipopolysaccharide) LPS-induced RAW 264.7 macrophages. T14 showed the strongest TRPV1 inhibition; T14 (200 μM) inhibited Ca²⁺ in capsaicin-stimulated HaCaT cells by 73.1% and showed stable binding in molecular docking, warranting further analysis. Mechanistic studies revealed that T14 suppressed NF-κB signaling by downregulating p65 protein expression, thereby reducing pro-inflammatory cytokine secretion (G-CSF, GM-CSF, ICAM-1, IL-6, TNF-α) in RAW 264.7 cells. Additionally, T14 (400 μM) inhibited ET-1 in LPS-stimulated endothelial cells by 75.0%; ICAM-1 reached 49.0%. Network pharmacology predicted STAT3, MAPK3, SPHK1, and CTSB as key targets mediating T14’s effects. These study findings suggest that T14 may be a promising candidate for skincare applications targeting SS. Full article

(This article belongs to the Special Issue Bioactive Compounds from Marine Fish)

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15 pages, 3992 KiB

Open AccessArticle

The Mediterranean Sea on the Bench: Unveiling the Marine Invertebrate Sidnyum elegans as a Source of Novel Promising Therapeutic Tools Against Triple-Negative Breast Cancer

by Marcello Casertano, Camilla Esposito, Ivana Bello, Martina Barile, Luana Izzo, Emma Mitidieri, Raffaella Sorrentino, Marialuisa Menna, Elisabetta Panza, Concetta Imperatore and Roberta d’Emmanuele di Villa Bianca

Mar. Drugs 2025, 23(5), 195; https://doi.org/10.3390/md23050195 - 29 Apr 2025

Viewed by 736

Abstract

This study aims to unveil the marine invertebrate Sidnyum elegans, a Mediterranean ascidian, as a natural resource for the early development of new treatments for triple-negative breast cancer (TNBC). Nine different fractions obtained via medium-pressure liquid chromatography (MPLC) of the butanol-soluble [...] Read more.

This study aims to unveil the marine invertebrate Sidnyum elegans, a Mediterranean ascidian, as a natural resource for the early development of new treatments for triple-negative breast cancer (TNBC). Nine different fractions obtained via medium-pressure liquid chromatography (MPLC) of the butanol-soluble material of the ascidian were evaluated in proliferating MDA-MB-231 cells in a range of 10–50 µg/mL. Among them, the SEB-5 fraction was found to be the most effective in reducing cell proliferation and concomitantly inducing apoptosis, revealed via MTT assay and FACS analysis using Annexin V/PI dual staining. Furthermore, we investigated the effect of this fraction on cell cycle phases, revealing that SEB-5 can arrest the cells in the G0/G1 phase. This latter effect was then confirmed via transcriptomic analysis, showing that treatment with SEB-5 reduced the expression of cyclinB1, CDC25a, and CDK1. Finally, to evaluate the potential antimetastatic effect of SEB-5, a wound-healing assay was performed showing the ability of SEB-5 to reduce MDA-MB-231 cell migration. The chemical characterization of SEB-5 components was performed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS) and nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed the presence of a terpenoid and polyketide-like compounds, including the alkyl sulfate 1 and phosphoeleganin 2, along with three novel phosphoeleganin-related products 3–5. Full article

(This article belongs to the Special Issue Perspectives for the Development of New Multitarget Marine Drugs)

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20 pages, 5265 KiB

Open AccessArticle

Isolation and Characterization of L-Asparaginase-Producing Bacteria from the Arabian–Persian Gulf Region: First Report on Bacillus xiamenensis ASP-J1-4 as a Producer and Its Potential Application

by Ghofran M. Al-Harbi, Essam Kotb, Abeer A. Almiman, Mahmoud M. Berekaa, Salwa Alhamad, Nada F. Alahmady, Meneerah A. Aljafary, Nadiyah M. Alqazlan, Reem I. Alyami, Joud M. Alqarni and Ebtesam Abdullah Al-Suhaimi

Mar. Drugs 2025, 23(5), 194; https://doi.org/10.3390/md23050194 - 29 Apr 2025

Viewed by 877

Abstract

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the [...] Read more.

L-asparaginase (L-ASNase) functions as a chemotherapeutic enzyme with antitumor properties. It facilitates the degradation of L-asparagine (L-ASN), a vital amino acid required for the proliferation of tumor cells. In this study, we have isolated 177 L-ASNase-producing strains from the aquatic environment of the Arabian–Persian Gulf. The most potent isolate, ASP-J1-4, was an endophyte recovered from the seablite Suaeda maritima and was molecularly identified as B. xiamenensis (accession number PQ593941). The enzyme purified through DEAE-Sepharose displayed a molecular weight of 37 kDa based on the SDS-PAGE profile and lacked detectable L-glutaminase (L-GTNase) activity. Optimal enzyme activity was at 40 °C and pH 9.0, with stability at pH 7–9. The maximum stimulation effect was found in the presence of Fe³⁺, Mn²⁺, and Na⁺ ions, respectively. The enzyme demonstrated a V_max of 35.71 U/mL and a K_m of 0.15 mM. Interestingly, ASP-J1-4 L-ASNase showed a dose-dependent inhibition against human colon carcinoma (HCT-116) and cervical Henrietta Lacks (HeLa) cell lines, with IC₅₀ values of 15.42 µg/mL and 12.13 µg/mL, respectively. These findings collectively suggest a biocompatible, efficient, and robust enzyme for potential applications in tumor therapy after validation of in vivo studies and clinical trials. This study introduces the first deep screening program for L-ASNase-producing bacteria harboring in the Arabian–Persian Gulf region. In addition, it launches B. xiamenensis and other species as new sources of L-ASNase. Full article

(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)

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19 pages, 2194 KiB

Open AccessArticle

Metabolite Profiling and Antioxidant Activities in Seagrass Biomass

by Pilar Garcia-Jimenez, Milagros Rico, Diana del Rosario-Santana, Vicent Arbona, Marina Carrasco-Acosta and David Osca

Mar. Drugs 2025, 23(5), 193; https://doi.org/10.3390/md23050193 - 29 Apr 2025

Viewed by 1086

Abstract

In this work, metabolite profiling of seeds and antioxidant analysis of fragments of two marine seagrasses, Posidonia oceanica and Cymodocea nodosa, were carried out to identify metabolite signature involved in seed viability and to evaluate the potential of fragments as a source of [...] Read more.

In this work, metabolite profiling of seeds and antioxidant analysis of fragments of two marine seagrasses, Posidonia oceanica and Cymodocea nodosa, were carried out to identify metabolite signature involved in seed viability and to evaluate the potential of fragments as a source of bioactive compounds. Using HILIC/QTOF-MS, UHPLC-MS and spectrophotometric analysis, seed metabolites and polyphenols and antioxidant activities, such as those of radical scavenging (RSA), reduction (FRAP, CUPRAC) and complexation (CCA), of rhizome fragments were evaluated. Metabolite comparison between seeds revealed differences across development stages (germinated and non-germinated) and seed types (dormant and non-dormant), providing insights into metabolic activity potentially associated with germination processes and seed viability. Furthermore, polyphenol analysis showed the highest content of caffeic acid in mature leaves (17.00 ± 0.02 μg g⁻¹ dw for P. oceanica and 98.00 ± 0.03 μg g⁻¹ dw for C. nodosa). Total phenolic content was correlated with flavonoids and with reduction and complexation activities. The combination of radical scavenging activity and t_1/2 was higher in P. oceanica than C. nodosa and also surpassed the commercial synthetic antioxidant BHA. We conclude P. oceanica and C. nodosa exhibit distinct seed metabolite profiles related to germination and type of seeds, and that fragments are rich in antioxidants, with potential as sustainable sources of bioactive compounds. Full article

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

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6 pages, 178 KiB

Open AccessEditorial

Marine Bioactive Peptides—Structure, Function, and Application 2.0

by Bin Wang and Chang-Feng Chi

Mar. Drugs 2025, 23(5), 192; https://doi.org/10.3390/md23050192 - 28 Apr 2025

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Abstract

In recent years, people’s lifestyles have undergone relatively significant changes [...] Full article

(This article belongs to the Special Issue Marine Bioactive Peptides—Structure, Function, and Application 2.0)

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Mar. Drugs, Volume 23, Issue 5 (May 2025) – 42 articles

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