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

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

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

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

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

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

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

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

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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23 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

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

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

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

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

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

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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36 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

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

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

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

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

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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