Marine Drugs

20 pages, 9174 KiB

Open AccessReview

Marine-Derived Collagen and Chitosan: Perspectives on Applications Using the Lens of UN SDGs and Blue Bioeconomy Strategies

by Mariana Almeida and Helena Vieira

Mar. Drugs 2025, 23(8), 318; https://doi.org/10.3390/md23080318 (registering DOI) - 1 Aug 2025

Abstract

Marine biomass, particularly from waste streams, by-products, underutilized, invasive, or potential cultivable marine species, offers a sustainable source of high-value biopolymers such as collagen and chitin. These macromolecules have gained significant attention due to their biocompatibility, biodegradability, functional versatility, and broad applicability across [...] Read more.

Marine biomass, particularly from waste streams, by-products, underutilized, invasive, or potential cultivable marine species, offers a sustainable source of high-value biopolymers such as collagen and chitin. These macromolecules have gained significant attention due to their biocompatibility, biodegradability, functional versatility, and broad applicability across health, food, wellness, and environmental fields. This review highlights recent advances in the uses of marine-derived collagen and chitin/chitosan. In alignment with the United Nations Sustainable Development Goals (SDGs), we analyze how these applications contribute to sustainability, particularly in SDGs related to responsible consumption and production, good health and well-being, and life below water. Furthermore, we contextualize the advancement of product development using marine collagen and chitin/chitosan within the European Union’s Blue bioeconomy strategies, highlighting trends in scientific research and technological innovation through bibliometric and patent data. Finally, the review addresses challenges facing the development of robust value chains for these marine biopolymers, including collaboration, regulatory hurdles, supply-chain constraints, policy and financial support, education and training, and the need for integrated marine resource management. The paper concludes with recommendations for fostering innovation and sustainability in the valorization of these marine resources. Full article

(This article belongs to the Special Issue Innovative Biotechnology Processes for Marine By-Products: From Waste Stream to Value Stream)

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24 pages, 1165 KiB

Open AccessReview

Neoxanthin: A Promising Medicinal and Nutritional Carotenoid

by Jiarong Zhao, Gengjie Zhuang and Jinrong Zhang

Mar. Drugs 2025, 23(8), 317; https://doi.org/10.3390/md23080317 (registering DOI) - 1 Aug 2025

Abstract

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the [...] Read more.

Neoxanthin is a xanthophyll carotenoid with high-value nutritional functions for human health due to its anti-cancer, anti-oxidative, and anti-obesity activities. In this present work, we systematically reviewed the structure, source, and biosynthetic pathways of neoxanthin, and discussed the advantages and disadvantages of the prevailing extraction methods of neoxanthin. Meanwhile, this review described the latest research progress on the pharmacological activities of neoxanthin. Finally, we concluded with a discussion on the main challenges of neoxanthin production from microalgae, and proposed some future development prospects and potential solutions. Full article

(This article belongs to the Special Issue Marine Carotenoids and Potential Therapeutic Benefits)

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10 pages, 726 KiB

Open AccessArticle

Discovery of New Everninomicin Analogs from a Marine-Derived Micromonospora sp. by Metabolomics and Genomics Approaches

by Tae Hyun Lee, Nathan J. Brittin, Imraan Alas, Christopher D. Roberts, Shaurya Chanana, Doug R. Braun, Spencer S. Ericksen, Song Guo, Scott R. Rajski and Tim S. Bugni

Mar. Drugs 2025, 23(8), 316; https://doi.org/10.3390/md23080316 (registering DOI) - 31 Jul 2025

Abstract

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal [...] Read more.

During the course of genome mining initiatives, we identified a marine-derived Micromonospora, assigned here as strain WMMD956; the genome of WMMD956 appeared to contain a number of features associated with everninomicins, well-known antimicrobial orthosomycins. In addition, LCMS-based hierarchical clustering analysis and principal component analysis (hcapca) revealed that WMMD956 displayed an extreme degree of metabolomic and genomic novelty. Dereplication of high-resolution tandem mass spectrometry (HRMS/MS) and Global Natural Product Social molecular networking platform (GNPS) analysis of WMMD956 resulted in the identification of several analogs of the previously known everninomicin. Chemical structures were unambiguously confirmed by HR-ESI-MS, 1D and 2D NMR experiments, and the use of MS/MS data. The isolated metabolites, 1–3, were evaluated for their antibacterial activity against methicillin-resistant Staphalococcus aureus (MRSA). Full article

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

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35 pages, 1467 KiB

Open AccessReview

Marine Derived Strategies Against Neurodegeneration

by Vasileios Toulis, Gemma Marfany and Serena Mirra

Mar. Drugs 2025, 23(8), 315; https://doi.org/10.3390/md23080315 (registering DOI) - 31 Jul 2025

Abstract

Marine ecosystems are characterized by an immense biodiversity and represent a rich source of biological compounds with promising potential for the development of novel therapeutic drugs. This review describes the most promising marine-derived neuroprotective compounds with strong potential for the treatment of neurodegenerative [...] Read more.

Marine ecosystems are characterized by an immense biodiversity and represent a rich source of biological compounds with promising potential for the development of novel therapeutic drugs. This review describes the most promising marine-derived neuroprotective compounds with strong potential for the treatment of neurodegenerative disorders. We focus specifically on the retina and brain—two key components of the central nervous system—as primary targets for therapeutic interventions against neurodegeneration. Alzheimer’s disease and retinal degeneration diseases are used here as a representative model of neurodegenerative disorders, where complex molecular processes such as protein misfolding, oxidative stress, and neuroinflammation drive disease progression. We also examine gene therapy approaches inspired by marine biology, with particular attention to their application in retinal diseases, aimed at preserving or restoring photoreceptor function and vision. Full article

(This article belongs to the Special Issue Marine-Derived Novel Drugs in the Treatment of Alzheimer’s Disease)

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21 pages, 879 KiB

Open AccessArticle

Multiblock Metabolomics Responses of the Diatom Phaeodactylum tricornutum Under Benthic and Planktonic Culture Conditions

by Andrea Castaldi, Mohamed Nawfal Triba, Laurence Le Moyec, Cédric Hubas, Gaël Le Pennec and Marie-Lise Bourguet-Kondracki

Mar. Drugs 2025, 23(8), 314; https://doi.org/10.3390/md23080314 (registering DOI) - 31 Jul 2025

Abstract

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated [...] Read more.

This study investigates the metabolic responses of the model diatom Phaeodactylum tricornutum under different growth conditions, comparing benthic (adherent) and planktonic states. Using a multiblock metabolomics approach combining LC-HRMS², NMR, and GC-MS techniques, we compared the metabolome of P. tricornutum cultivated on three laboratory substrates (glass, polystyrene, and polydimethylsiloxane) and under planktonic conditions. Our results revealed metabolic differences between adherent and planktonic cultures, particularly concerning the lipid and carbohydrate contents. Adherent cultures showed a metabolic profile with an increase in betaine lipids (DGTA/S), fatty acids (tetradecanoic and octadecenoic acids), and sugars (myo-inositol and ribose), suggesting modifications in membrane composition and lipid remodeling, which play a potential role in adhesion. In contrast, planktonic cultures displayed a higher content of cellobiose, specialized metabolites such as dihydroactinidiolide, quinic acid, catechol, and terpenes like phytol, confirming different membrane composition, energy storage capacity, osmoregulation, and stress adaptation. The adaptative strategies do not only concern adherent and planktonic states, but also different adherent culture conditions, with variations in lipid, amino acid, terpene, and carbohydrate contents depending on the physical properties of the support. Our results highlight the importance of metabolic adaptation in adhesion, which could explain the fouling process. Full article

(This article belongs to the Special Issue Marine Omics for Drug Discovery and Development, 2nd Edition)

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18 pages, 8458 KiB

Open AccessArticle

Exploring the Biosynthetic Potential of Microorganisms from the South China Sea Cold Seep Using Culture-Dependent and Culture-Independent Approaches

by Gang-Ao Hu, Huai-Ying Sun, Qun-Jian Yin, He Wang, Shi-Yi Liu, Bin-Gui Wang, Hong Wang, Xin Li and Bin Wei

Mar. Drugs 2025, 23(8), 313; https://doi.org/10.3390/md23080313 - 30 Jul 2025

Abstract

Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, [...] Read more.

Cold seep ecosystems harbor unique microbial communities with potential for producing secondary metabolites. However, the metabolic potential of cold seep microorganisms in the South China Sea remains under-recognized. This study employed both culture-dependent and culture-independent approaches, including 16S rRNA amplicon sequencing and metagenomics, to investigate microbial communities and their potential for secondary metabolite production in the South China Sea cold seep. The results indicate microbial composition varied little between two non-reductive sediments but differed significantly from the reductive sediment, primarily due to Planctomycetes and Actinobacteria. Predicting the Secondary Metabolism Potential using Amplicon (PSMPA) predictions revealed 115 strains encoding more than 10 biosynthetic gene clusters (BGCs), with lower BGC abundance in reductive sediment. Culture-dependent studies showed Firmicutes as the dominant cultivable phylum, with strains from shallow samples encoding fewer BGCs. Metagenomic data confirmed distinct microbial compositions and BGC distributions across sediment types, with cold seep type having a stronger influence than geographic location. Certain BGCs showed strong correlations with sediment depth, reflecting microbial adaptation to nutrient-limited environments. This study provides a comprehensive analysis of the metabolic capabilities of South China Sea cold seep microorganisms and reveals key factors influencing their secondary metabolic potential, offering valuable insights for the efficient exploration of cold seep biological resources. Full article

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

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12 pages, 1849 KiB

Open AccessArticle

Dolabellane Diterpenoids from Soft Coral Clavularia viridis with Anti-Inflammatory Activities

by Chufan Gu, Hongli Jia, Kang Zhou, Bin Wang, Wenhan Lin and Wei Cheng

Mar. Drugs 2025, 23(8), 312; https://doi.org/10.3390/md23080312 (registering DOI) - 30 Jul 2025

Abstract

A chemical investigation of the EtOAc fraction from soft coral Clavularia viridis resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely clavirolides W–Z (1–4), clavularols A–H (5–12), and three known analogs (13– [...] Read more.

A chemical investigation of the EtOAc fraction from soft coral Clavularia viridis resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely clavirolides W–Z (1–4), clavularols A–H (5–12), and three known analogs (13–15). Their structures were characterized by an extensive analysis of spectroscopic data, including X-ray diffraction and ECD calculations for the assignment of absolute configurations. The structures of 2 and 4–6 are feathered as peroxyl-substituted derivatives, while compounds 7–12 possess additional oxidative cyclization, including epoxide or furan that are rare in the dolabellane family. All these compounds were evaluated for activities on cytotoxic and anti-inflammatory models. Compound 10 exhibited most potential against NO production in the BV2 cell induced by LPS with an IC₅₀ value of 18.3 μM. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

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21 pages, 2015 KiB

Open AccessArticle

Enhancing Fucoxanthin Pickering Emulsion Stability and Encapsulation with Seaweed Cellulose Nanofibrils Using High-Pressure Homogenization

by Ying Tuo, Mingrui Wang, Yiwei Yu, Yixiao Li, Xingyuan Hu, Long Wu, Zongpei Zhang, Hui Zhou and Xiang Li

Mar. Drugs 2025, 23(8), 311; https://doi.org/10.3390/md23080311 - 30 Jul 2025

Abstract

Poor solubility and bioavailability have limited the application of fucoxanthin in drug and functional food processing. In order to encapsulate fucoxanthin in delivery systems, in this study, cellulose was isolated from industrial brown algae residues and high-pressure homogenized into cellulose nanofibrils (CNFs). Then, [...] Read more.

Poor solubility and bioavailability have limited the application of fucoxanthin in drug and functional food processing. In order to encapsulate fucoxanthin in delivery systems, in this study, cellulose was isolated from industrial brown algae residues and high-pressure homogenized into cellulose nanofibrils (CNFs). Then, fucoxanthin was encapsulated into the Pickering emulsion stabilized by the CNFs. The effect of high-pressure homogenization on the characteristics of cellulose and the stability of fucoxanthin emulsion was evaluated. The results indicated that CNFs prepared at 105 MPa had a diameter of 87 nm and exhibited high zeta potential and thermal stability. Encapsulation efficiency peaked at 70.8% with 1.0 mg/mL fucoxanthin, and after three freeze–thaw cycles the encapsulation efficiency was higher than 60%. The DPPH scavenging activity after 12 days’ storage at 4 °C was still 42%. Furthermore, the Pickering emulsion with 1.0 mg/mL fucoxanthin showed high stability and antioxidant activity under different pH values, salinity, temperature, and UV light exposure duration. The CNFs effectively protected fucoxanthin from degradation, offering a novel delivery system for marine bioactive compounds. To the best of our knowledge, this is the first study on the fucoxanthin delivery system of Pickering emulsion stabilized by the CNFs. Such emulsion might benefit the encapsulation and release of bioactive components in marine drugs. Full article

(This article belongs to the Special Issue Marine Carotenoids: Properties, Health Benefits, and Applications)

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42 pages, 2457 KiB

Open AccessReview

Therapeutic Potential of Sea Cucumber-Derived Bioactives in the Prevention and Management of Brain-Related Disorders: A Comprehensive Review

by Purnima Rani Debi, Hrishika Barua, Mirja Kaizer Ahmmed and Shuva Bhowmik

Mar. Drugs 2025, 23(8), 310; https://doi.org/10.3390/md23080310 - 30 Jul 2025

Abstract

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being [...] Read more.

The popularity of bioactive compounds extracted from sea cucumbers is growing due to their wide application in the pharmaceutical industry, particularly in the development of drugs for neurological disorders. Different types of compounds, such as saponins, phenolic compounds, cerebrosides, and glucocerebrosides, are being studied intensively for their efficacy in assessing the treatment of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and brain tumors, among others. Positive results have been observed in the upregulation in the content of p-CREB, p-PL3K, BDNF, SOD, and MDA. Furthermore, the neuroprotective mechanism of the compounds against Alzheimer’s disease revealed that suppressing the phosphorylation of tau protein by the PI3K/Akt/GSK3β pathway leads to improved synaptic plasticity and reduced nerve fiber tangles. This comprehensive review explores recent findings on the therapeutic potential of sea cucumber bioactives in the treatment of brain-related disorders. Full article

(This article belongs to the Special Issue Effects of Marine Natural Products in Brain Health and Metabolic Diseases)

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18 pages, 4455 KiB

Open AccessArticle

Spermine Promotes the Formation of Conchosporangia in Pyropia haitanensis Through Superoxide Anions

by Tingting Niu, Haike Qian, Lufan Cheng, Qijun Luo, Juanjuan Chen, Rui Yang, Peng Zhang, Tiegan Wang and Haimin Chen

Mar. Drugs 2025, 23(8), 309; https://doi.org/10.3390/md23080309 - 30 Jul 2025

Abstract

The transition from conchocelis to conchosporangia in Pyropia haitanensis represents a pivotal stage in its life cycle. As a commercially vital red alga, P. haitanensis plays a dominant role in global nori production. The transition governing its sporulation efficiency is pivotal for aquaculture [...] Read more.

The transition from conchocelis to conchosporangia in Pyropia haitanensis represents a pivotal stage in its life cycle. As a commercially vital red alga, P. haitanensis plays a dominant role in global nori production. The transition governing its sporulation efficiency is pivotal for aquaculture success, yet the underlying regulatory mechanisms, especially their integration with metabolic cues such as polyamines, remain poorly understood. This study uncovered a critical role for the polyamine spermine (SPM) in promoting conchosporangial formation, mediated through the signaling activity of superoxide anions (O₂·⁻). Treatment with SPM markedly elevated O₂·⁻ levels, an effect that was effectively inhibited by the NADPH oxidase inhibitor diphenyliodonium chloride (DPI), underscoring the role of O₂·⁻ as a key signaling molecule. Transcriptomic analysis revealed that SPM enhanced photosynthesis, carbon assimilation, and respiratory metabolism, while simultaneously activating antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT), to regulate hydrogen peroxide (H₂O₂) levels and maintain redox homeostasis. Furthermore, SPM upregulated genes associated with photosynthetic carbon fixation and the C₂ oxidative photorespiration pathway, supplying the energy and metabolic resources necessary for this developmental transition. These findings suggested that SPM orchestrated O₂·⁻ signaling, photosynthetic activity, and antioxidant defenses to facilitate the transition from conchocelis to conchosporangia in P. haitanensis. Full article

(This article belongs to the Section Marine Chemoecology for Drug Discovery)

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15 pages, 1527 KiB

Open AccessArticle

Marine-Inspired Ovothiol Analogs Inhibit Membrane-Bound Gamma-Glutamyl-Transpeptidase and Modulate Reactive Oxygen Species and Glutathione Levels in Human Leukemic Cells

by Annalisa Zuccarotto, Maria Russo, Annamaria Di Giacomo, Alessandra Casale, Aleksandra Mitrić, Serena Leone, Gian Luigi Russo and Immacolata Castellano

Mar. Drugs 2025, 23(8), 308; https://doi.org/10.3390/md23080308 - 30 Jul 2025

Abstract

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance [...] Read more.

The enzyme γ-glutamyl transpeptidase (GGT), located on the surface of cellular membranes, hydrolyzes extracellular glutathione (GSH) to guarantee the recycling of cysteine and maintain intracellular redox homeostasis. High expression levels of GGT on tumor cells are associated with increased cell proliferation and resistance against chemotherapy. Therefore, GGT inhibitors have potential as adjuvants in treating GGT-positive tumors; however, most have been abandoned during clinical trials due to toxicity. Recent studies indicate marine-derived ovothiols as more potent non-competitive GGT inhibitors, inducing a mixed cell-death phenotype of apoptosis and autophagy in GGT-overexpressing cell lines, such as the chronic B leukemic cell HG-3, while displaying no toxicity towards non-proliferative cells. In this work, we characterize the activity of two synthetic ovothiol analogs, L-5-sulfanylhistidine and iso-ovothiol A, in GGT-positive cells, such as HG-3 and HL-60 cells derived from acute promyelocytic leukemia. The two compounds inhibit the activity of membrane-bound GGT, without altering cell vitality nor inducing cytotoxic autophagy in HG-3 cells. We provide evidence that a portion of L-5-sulfanylhistidine enters HG-3 cells and acts as a redox regulator, contributing to the increase in intracellular GSH. On the other hand, ovothiol A, which is mostly sequestered by external membrane-bound GGT, induces intracellular ROS increase and the consequent autophagic pathways. These findings provide the basis for developing ovothiol derivatives as adjuvants in treating GGT-positive tumors’ chemoresistance. Full article

(This article belongs to the Special Issue Marine-Derived Novel Antioxidants)

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15 pages, 3436 KiB

Open AccessArticle

Mohangic Acid H and Mohangiol: New p-Aminoacetophenone Derivatives from a Mudflat-Derived Streptomyces sp.

by Juwan Son, Ju Heon Lee, Yong-Joon Cho, Kyuho Moon and Munhyung Bae

Mar. Drugs 2025, 23(8), 307; https://doi.org/10.3390/md23080307 - 30 Jul 2025

Abstract

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established [...] Read more.

Streptomyces sp. AWH31-250, isolated from a tidal mudflat in the Nakdong River estuary in Busan, Republic of Korea, was found to produce two novel p-aminoacetophenone derivatives, mohangic acid H (1) and mohangiol (2). Their planar structures were established by comprehensive 1D and 2D NMR spectroscopy, mass spectrometry, and UV analysis, possessing a shorter carbon-chain with a diene moiety, whereas known mohangic acids A–F bear a longer carbon-chain with a triene moiety. The absolute configurations of the key stereogenic centers were determined via computational DP4+ calculations and bioinformatic analysis of the ketoreductase domain sequence from the biosynthetic gene cluster. Based on the careful gene analysis along with whole-genome sequencing, the first plausible biosynthetic pathway of mohangic acids A–G and mohangiol was proposed. Mohangic acid H (1) and mohangiol (2) displayed moderate inhibitory activity against Candida albicans isocitrate lyase with IC₅₀ values of 21.37 and 21.12 µg/mL, respectively. Full article

(This article belongs to the Section Structural Studies on Marine Natural Products)

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11 pages, 2255 KiB

Open AccessArticle

Potential Inhibitors of Human–Naegleria fowleri Interactions: An In Vitro Extracellular Matrix-Based Model

by Javier Chao-Pellicer, Iñigo Arberas-Jiménez, Ines Sifaoui, Ana R. Díaz-Marrero, José J. Fernández, Melissa Jamerson, José E. Piñero and Jacob Lorenzo-Morales

Mar. Drugs 2025, 23(8), 306; https://doi.org/10.3390/md23080306 - 30 Jul 2025

Abstract

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success [...] Read more.

Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti-Naegleria activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the N. fowleri trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against N. fowleri infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host–pathogen interactions critical to PAM pathogenesis. Full article

(This article belongs to the Special Issue Marine Antiparasitic Agents, 2nd Edition)

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13 pages, 570 KiB

Open AccessReview

Examples of Underexploited Marine Organisms in Cosmeceutical Applications

by Céline Couteau and Laurence Coiffard

Mar. Drugs 2025, 23(8), 305; https://doi.org/10.3390/md23080305 - 30 Jul 2025

Abstract

A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of [...] Read more.

A number of marine resources have been exploited for a long time. Examples include Fucus and Laminaria, from which gelling agents are extracted. Only a few hundred thousand marine species are currently known, representing a tiny fraction of the estimated total of between 700,000 and one million species. This opens up numerous possibilities for innovation in the cosmetics industry. In this study, we present various species that are currently under-exploited, but which could have applications in hydration and photoprotection, for example. Algae and microalgae are worthy of interest because they can be used for hydration and anti-ageing purposes. Collagen can be extracted from animal sources and used as a substitute for collagen of bovine origin. From a marketing perspective, it is possible to market it as ‘marine collagen’. However, it is imperative to emphasize the significance of ensuring the sustainability of the resource. In accordance with this imperative, algae that are capable of being cultivated are distinguished by their enhanced qualities. Full article

(This article belongs to the Section Marine-Derived Ingredients for Drugs, Cosmeceuticals and Nutraceuticals)

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19 pages, 4058 KiB

Open AccessArticle

Antitumor Activity of Ruditapes philippinarum Polysaccharides Through Mitochondrial Apoptosis in Cellular and Zebrafish Models

by Mengyue Liu, Weixia Wang, Haoran Wang, Shuang Zhao, Dongli Yin, Haijun Zhang, Chunze Zou, Shengcan Zou, Jia Yu and Yuxi Wei

Mar. Drugs 2025, 23(8), 304; https://doi.org/10.3390/md23080304 - 29 Jul 2025

Abstract

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this [...] Read more.

Colorectal cancer (CRC) remains a predominant cause of global cancer-related mortality, highlighting the pressing demand for innovative therapeutic strategies. Natural polysaccharides have emerged as promising candidates in cancer research due to their multifaceted anticancer mechanisms and tumor-suppressive potential across diverse malignancies. In this study, we enzymatically extracted a polysaccharide, named ERPP, from Ruditapes philippinarum and comprehensively evaluated its anti-colorectal cancer activity. We conducted in vitro assays, including CCK-8 proliferation, clonogenic survival, scratch wound healing, and Annexin V-FITC/PI apoptosis staining, and the results demonstrated that ERPP significantly inhibited HT-29 cell proliferation, suppressed colony formation, impaired migratory capacity, and induced apoptosis. JC-1 fluorescence assays provided further evidence of mitochondrial membrane potential (MMP) depolarization, as manifested by a substantial reduction in the red/green fluorescence ratio (from 10.87 to 0.35). These antitumor effects were further validated in vivo using a zebrafish HT-29 xenograft model. Furthermore, ERPP treatment significantly attenuated tumor angiogenesis and downregulated the expression of the vascular endothelial growth factor A (Vegfaa) gene in the zebrafish xenograft model. Mechanistic investigations revealed that ERPP primarily activated the mitochondrial apoptosis pathway. RT-qPCR analysis showed an upregulation of the pro-apoptotic gene Bax and a downregulation of the anti-apoptotic gene Bcl-2, leading to cytochrome c (CYCS) release and caspase-3 (CASP-3) activation. Additionally, ERPP exhibited potent antioxidant capacity, achieving an 80.2% hydroxyl radical scavenging rate at 4 mg/mL. ERPP also decreased reactive oxygen species (ROS) levels within the tumor cells, thereby augmenting anticancer efficacy through its antioxidant activity. Collectively, these findings provide mechanistic insights into the properties of ERPP, underscoring its potential as a functional food component or adjuvant therapy for colorectal cancer management. Full article

(This article belongs to the Special Issue Isolation, Identification and Applications of Marine Source Polysaccharides and Peptides—2nd Edition)

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21 pages, 576 KiB

Open AccessReview

Role of Enzyme Technologies and Applied Enzymology in Valorising Seaweed Bioproducts

by Blessing Mabate, Lithalethu Mkabayi, Deandra Rochelle Goddard, Coleen Elizabeth Grobler and Brett Ivan Pletschke

Mar. Drugs 2025, 23(8), 303; https://doi.org/10.3390/md23080303 - 29 Jul 2025

Abstract

Seaweeds, classified as non-vascular plants, have definite advantages over terrestrial plants as they grow rapidly, can be cultivated in coastal environments, and are dependable and non-endangered sources of biomass. Algal bioproducts, which include a wide range of bioactive compounds, have drawn much interest [...] Read more.

Seaweeds, classified as non-vascular plants, have definite advantages over terrestrial plants as they grow rapidly, can be cultivated in coastal environments, and are dependable and non-endangered sources of biomass. Algal bioproducts, which include a wide range of bioactive compounds, have drawn much interest because of their applications in nutraceuticals, pharmaceuticals, agriculture, and cosmetics. Particularly in the pharmaceutical and nutraceutical fields, algal bioproducts have shown tremendous activity in regulating enzymes involved in human diseases. However, the drawbacks of conventional extraction methods impede the complete exploitation of seaweed biomass. These include low efficiency, high cost, and potential harm to the environment. Enzyme technology developments in recent years present a viable way to overcome these challenges. Enzymatic processes improve product yields and reduce the environmental impact of processing, while facilitating the more effective extraction of valuable bioactive compounds as part of an integrated biorefinery approach. Enzyme-assisted biorefinery techniques can greatly advance the creation of a circular bioeconomy and increase the yield of extracted seaweed bioproducts, thus improving their value. With the potential to scale up to industrial levels, these biotechnological developments in enzymatic extraction are developing rapidly and can advance the sustainable exploitation of seaweed resources. This review emphasises the increasing importance of enzyme technologies in the seaweed biorefinery and their contribution to developing more environmentally friendly, economically feasible, and sustainable methods for valorising products derived from seaweed. In the biorefinery industry, enzyme-assisted methods have enormous potential for large-scale industrial applications with further development, opening the door to a more sustainable, circular bioeconomy. Full article

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

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18 pages, 2342 KiB

Open AccessArticle

Simplified, High Yielding Extraction of Xylan/Xylo-Oligosaccharides from Palmaria palmata: The Importance of the Algae Preservation Treatment

by Diogo Coelho, Diogo Félix Costa, Mário Barroca, Sara Alexandra Cunha, Maria Manuela Pintado, Helena Abreu, Margarida Martins and Tony Collins

Mar. Drugs 2025, 23(8), 302; https://doi.org/10.3390/md23080302 - 29 Jul 2025

Abstract

The complex plant cell wall heteropolysaccharide xylan, and its breakdown products xylo-oligosaccharides and xylose, are value-added compounds with a plethora of potential applications in diverse areas. They are nonetheless currently poorly exploited, with a major bottleneck being the unavailability of efficient, low-cost, high-yield [...] Read more.

The complex plant cell wall heteropolysaccharide xylan, and its breakdown products xylo-oligosaccharides and xylose, are value-added compounds with a plethora of potential applications in diverse areas. They are nonetheless currently poorly exploited, with a major bottleneck being the unavailability of efficient, low-cost, high-yield production processes. The major objective of the present study is to identify and characterise a high-yield process for the preparation of highly pure xylan/XOS products from the macroalga Palmaria palmata. Currently, most xylan is extracted from land-sourced lignocellulosic feedstocks, but we take advantage of the high xylan content, xylan aqueous solubility, lignin-free nature, weakly linked cell wall matrix, and sustainability of the macroalga to identify a simple, sustainable, high-yield, novel-xylan-structure extraction process. This is composed of five steps: alga oven drying, milling, aqueous extraction, centrifugation, and dialysis, and we show that the alga preservation step plays a critical role in component extractability, with oven drying at high temperatures, ~100 °C, enhancing the subsequent aqueous extraction process, and providing for xylan yields as high as 80% of a highly pure (~90%) xylan product. The process developed herein and the insights gained will promote a greater availability of these bioactive compounds and open up their application potential. Full article

(This article belongs to the Special Issue Eco-Friendly Extraction and Applications of Bioactive Compounds from Marine Algae)

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15 pages, 2504 KiB

Open AccessReview

The Madangamines: Synthetic Strategies Toward Architecturally Complex Alkaloids

by Valentina Ríos, Cristian Maulen, Claudio Parra and Ben Bradshaw

Mar. Drugs 2025, 23(8), 301; https://doi.org/10.3390/md23080301 - 28 Jul 2025

Abstract

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven [...] Read more.

Madangamine alkaloids have attracted considerable interest in the scientific community due to their complex polycyclic structures and potent biological activities. The six members identified to date have exhibited diverse and significant cytotoxic activities against various cancer cell lines. Despite their structural complexity, seven total syntheses—covering five of the six members—have been reported to date. These syntheses, involving 28 to 36 steps and global yields ranging from 0.006% to 0.029%, highlight the formidable challenge these compounds present. This review summarizes the key synthetic strategies developed to access critical fragments, including the construction of the ABC diazatricyclic core and the ACE ring systems. Approaches to assembling the ABCD and ABCE tetracyclic frameworks are also discussed. Finally, we highlight the completed total syntheses of madangamines A–E, with a focus on pivotal transformations and strategic innovations that have enabled progress in this field. Full article

(This article belongs to the Special Issue Discovery, Synthesis and Mechanism of Marine Drugs for Treating Cancer)

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40 pages, 3124 KiB

Open AccessReview

Structural Diversity and Bioactivities of Marine Fungal Terpenoids (2020–2024)

by Minghua Jiang, Senhua Chen, Zhibin Zhang, Yiwen Xiao, Du Zhu and Lan Liu

Mar. Drugs 2025, 23(8), 300; https://doi.org/10.3390/md23080300 - 27 Jul 2025

Abstract

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, [...] Read more.

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, and triterpenes) isolated from 104 fungal strains across 33 genera. Sesquiterpenoids and diterpenoids constitute the predominant chemical classes, with Trichoderma, Aspergillus, Eutypella, and Penicillium being the most productive genera. These fungi were primarily sourced from distinct marine niches, including deep sea sediments, algal associations, mangrove ecosystems, and invertebrate symbioses. Notably, 57% of the 266 tested compounds exhibited diverse biological activities, encompassing anti-inflammatory, antibacterial, antimicroalgal, antifungal, cytotoxic effects, etc. The chemical diversity and biological activities of these marine fungal terpenoids underscore their value as promising lead compounds for pharmaceutical development. Full article

(This article belongs to the Special Issue Diversity of Marine Fungi as a Source of Bioactive Natural Products, 3rd Edition)

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Marine Drugs

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